!   "

#   $   !     % % & ' ( ) * (

+ , - . / 0 1 2 3 4 + 5 6 7 8 9 8

, : : 1 2 3 4 7 6 ; ; 9 <

+ . = 3 4 > . / 0 ? 8 @ 6 A 7 9

> B > C D E F + G >

H I J K 3 0 = 4 > L 0 M 1J I

= . N O M , / 1

J

M 3 P Q 1 / P

I

M . = O 1 N R 1 / D 3 S O T = / . = O 1 N D 3 U O 3 V

W 1 4 F 3 O M E N 2 3 / T 1 N X : ? O 3 R

- 3 N E T Y O N X : ? 3 P O 0 . M D 3 U O 3 V > . N . S 3 /

D O T Y > . N . S 3 P 3 N = . N 2 Z P [ M 3 P 3 N = . = O 1 N - / . N 0 ? 7

, 3 T = O 0 O 2 3 D 3 \ 3 U . M I. = O 1 N + O U O T O 1 N

W ? / 1

I

S ? 4 + . N .

H [ . = ] X - / . N 0 ? : ? O 3 R

B N U O / 1 N P 3 N = . M D O T Y - / . N 0 ? Z Z Z

B N U O / 1 N P 3 N = . M Q . = 3 . N 2 B R R 3 0 = T + O U O T O 1 N

Q / 1 P 4 > 3 M . N O 3 - O T 0 1 3 X > B > X , ? L T O 0 . M H0 O 3 N = O T =

: 1 M M 3 3 N > @ D 1 T T P 3 O T M X + ^ > X - O 1 M 1 S O T =

B N U O / 1 N P 3 N = . M D O T Y - / . N 0 ? Z Z Z

B N U O / 1 N P 3 N = . M Q . = 3 . N 2 B R R 3 0 = T + O U O T O 1 N

, 3 3 / D 3 U O 3 V 4 D 1 T . N N . _ 1 I O 3 \ ` I ] V O . Y X D O T Y E T T 3 T T P 3 N = , / 1 0 3 T T _ 3 . 2 3 /

> 3 M O T T . , . N S 3 / X , ? @ + @ X H 3 N O 1 / - O 1 M 1 S O T =

` . P 3 T a 3 = / O 0 Y X , ? @ + @ X H 3 N O 1 / H0 O 3 N 0 3 E 2 U O T 1 /

B N U O / 1 N P 3 N = . M D O T Y - / . N 0 ? Z Z Z

B N U O / 1 N P 3 N = . M Q . = 3 . N 2 B R R 3 0 = T + O U O T O 1 N

W ? 3 B N U O / 1 N P 3 N = . M Q . = 3 . N 2 B R R 3 0 = T + O U O T O 1 N b B Q B + c ? . T 0 1 P [ M 3 = 3 2 = ? 3 [ / 3 M O P O N . / L [ / 1

J

M 3 P

R 1 / P

I

M . = O 1 N b . = = . 0 ? 3 2 c R 1 / = ? 3 3 0 1 M 1 S O 0 . M / O T Y . N 2 2 / O N Y O N S V . = 3 / 3 d [ 1 T I/ 3 . T T 3 T T P 3 N = T = 1

J

3

0 1 N 2 I0 = 3 2 . T [ . / = 1 R = ? 3 D 3 S O T = / . = O 1 N D 3 U O 3 V 1 R = ? 3 R IN S O 0 O 2 3 P L 0 M 1 J I= . N O M b , : : 1 2 3 7 6 ; ; 9 < c @

W ? O T 2 1 0 I P 3 N = O T O N = 3 N 2 3 2 = 1 [ / 1 U O 2 3 . N 1 U 3 / U O 3 V 1 R V ? . = O T 0 I/ / 3 N = M L Y N 1 V N / 3 S . / 2 O N S = ? 3

3 N U O / 1 N P 3 N = . M R . = 3 . N 2 3 0 1 M 1 S O 0 . M 3 R R 3 0 = T . T T 1 0 O . = 3 2 V O = ? P L 0 M 1 J I

= . N O M . N 2 O = T 2 3 S / . 2 . = O 1 N

[ / 1 2 I0 = T X . N 2 1 I= M O N 3 T IN 0 3 / = . O N = O 3 T / 3 S . / 2 O N S . = = / O J I= 3 T 1 R = ? 3 [ . / 3 N = 0 1 P [ 1 IN 2 . N 2 O = T

= / . N T R 1 / P . = O 1 N [ / 1 2 I 0 = T @ Z = 2 3 T 0 / O J 3 T = ? 3 [ / 3 M O P O N . / L 3 0 1 M 1 S O 0 . M / O T Y ? L [ 1 = ? 3 T O T . N 2 = ? 3

[ / 1 0 3 T T 3 T = ? . = V O M M J 3 I T 3 2 2 I / O N S = ? 3 0 1 P [ M 3 = O 1 N 1 R = ? 3 [ / 3 M O P O N . / L 3 0 1 M 1 S O 0 . M / O T Y . T T 3 T T P 3 N =

O N T I[ [ 1 / = 1 R D 3 S O T = / . = O 1 N D 3 U O 3 V @

E T N 1 = 3 2 O N H 3 0 = O 1 N 9 X . 2 2 O = O 1 N . M 2 . = . V O M M J 3 N 3 3 2 3 2 R 1 / = ? 3 = 1 d O 0 1 M 1 S O 0 . M [ / 1 [ 3 / = O 3 T 1 R

P L 0 M 1 J I= . N O M = 1 0 1 P [ M 3 = 3 = ? 3 / O T Y . T T 3 T T P 3 N = . N 2 / 3 S O T = / . = O 1 N / 3 U O 3 V [ / 1 0 3 T T @ E 2 2 O = O 1 N . M

T = I2 O 3 T B Q B + / 3 0 1 P P 3 N 2 T J3 / 3 e I3 T = 3 2 O N 0 M I2 3 . U O . N . 0 I= 3 1 / . M . N 2 ? 1 N 3 L J3 3 = 1 d O 0 O = L T = I2 O 3 T X

f g h i j k l m j

2015.03.10 

08:50:19 -04'00'

JAMES HETRICK

Digitally signed by JAMES HETRICK 

DN: c=US, o=U.S. Government, ou=USEPA, 

ou=Staff, cn=JAMES HETRICK, 

dnQualifier=0000005599 

Date: 2015.03.10 16:35:20 -04'00'

ROSANNA LOUIEJUZWIAK 

2015.03.11 08:18:50 

-04'00'
Page 2 of 62

estuarine/marine invertebrate studies, freshwater fish studies, aquatic (vascular and nonvascular) plant and terrestrial plant studies. 

Additional fate and transport studies are not being requested for myclobutanil because a 

reasonably conservative risk assessment can be conducted with existing data gaps; however, 

additional fate data could assist in refining the assessment. 

Many of the myclobutanil product labels do not specify the maximum number of applications 

that can be applied per year or crop cycle and/or the number of crop cycles per year. Some 

labels are missing a single maximum application rate. We request that in completing the Use 

Summary Table, the registrants provide this information.

INTRODUCTION 

Myclobutanil is a systemic fungicide used to control powdery mildew on a number of crops. It is 

a triazole fungicide in the conazole class of fungicides. Myclobutanil is classified as a sterol 

biosynthesis inhibitor (SBI) and is further classified as a demethylation inhibitor (DMI) fungicide 

because it inhibits the enzyme sterol 14-demethylase, which disrupts the ergosterol 

biosynthesis pathway that is vital to fungal cell wall structure and function (FRAC 2012, Roberts 

and Hutson 1999). Myclobutanil is a Group 3 Fungicide. 

Myclobutanil was first registered in the United States in 1984. Based on the Summary Level 

Usage Analysis (SLUA) report, between 2004 -2012, the agricultural use with the highest usage 

(in pounds a.i. applied per year) is grapes with 50,000 average pounds used. The next highest 

usage crops were apples (20,000 average pounds per year) then almonds, tomatoes, and 

cherries with 8,000, 7,000, and 5,000 pounds used per year, respectively. Usage data are 

currently not available for the non-agricultural uses of myclobutanil.

All current labeled uses of myclobutanil include the following food uses: almond, apple, apricot, 

artichoke, asparagus, beans (succulent), blackberry, boysenberry, caneberries, canistel, carrot 

(including tops), cherry, chrysanthemum garland, cotton, cucurbits (pumpkin, squash, 

watermelon), currant, eggplant, gooseberry, grapes, hops, lettuce (head, leaf), loganberry, 

mamey (mammee apple), mango, mayhaw (Hawthorn), mint/peppermint/spearmint, 

nectarines, okra, olallie berries, papaya, peach, pepper, pimento, plum, prune, raspberry (black, 

red), sapodilla, sapote white, soybeans (unspecified), star apple, strawberry, subtropical/tropical 

fruit and tomato. Non-food/non-feed uses include bluegrass, commercial/industrial lawns, 

cotton (seed), Douglas Fir (seed orchard, shelter belt), golf course turf, grasses grown for seed, 

household/domestic dwellings (outdoor premises), hybrid cottonwood/poplar plantations, 

loblolly pine (forest), ornamental and shade trees, ornamentals (herbaceous plants, lawns and 

turf, sod farm (turf), unspecified, woody shrubs and vines), residential lawns and slash pine 

forest (USEPA 2014 a.). 

Application types include broadcast (aerial and ground), chemigation, directed spray, foliar 

treatment, ground spray, high volume spray (dilute), low volume spray (concentrate), seed 

treatment, spot treatment, and spray (USEPA 2014 a.).

Based on current labels, the maximum single application rate ranges from 0.1037 to 1.4 pounds 

of active ingredient per acre (lb a.i./acre) and up to 16 applications per year for some uses. The 
Page 3 of 62

highest annual application rates generally are found in the ornamentals (sod farms, lawns and 

turf) and residential lawns. However, the number of applications of myclobutanil that can be 

applied per calendar year or the maximum annual application rate for a given use is not 

explicitly stated on many of the current labels. 

The chemical profile produced by BEAD, located in the docket, lists the use patterns of 

maximum exposures for the current uses of Myclobutanil. EFED will use application scenarios 

that result in maximum exposure scenarios for a given use for the risk assessment. Any absence 

of information on the labels that specifies the maximum single application rate, the application 

interval, the annual maximum rate allowed (lb a.i./year), or application method may result in 

conservative assumptions.

Previous Ecological Assessments 

Myclobutanil has been assessed a number of times for new uses including Section 18 

assessments since the original registration in 1984. Such assessments include a 2009 California 

Red-Legged Frog Endangered Species Assessment and Section 3 Ecological Risk Assessment for 

Myclobutanil (October 12, 2007) (DP336613). EFED evaluated these assessments and others for 

myclobutanil in association with the current toxicity, exposure, and use information to 

determine if sufficient data are available and if further updates are needed to support 

registration review. In some of the previous assessments, risks were assessed using the parent 

compound only, whereas others took into consideration degradates of concern using the total 

toxic residue (TTR) approach. In the most recent assessment conducted in 2012, stressors of 

concern for aquatic organisms were considered to be myclobutanil and 1,2,4-triazole, while 

stressors of concern for terrestrial organisms were considered to be myclobutanil, the plant 

metabolite RH-9090, 1,2,4-triazole, and triazole conjugates 1,2,4-triazole alanine and 1,2,4 

triazole acetic acid (also referred to as triazole alanine and triazole acetic acid) (D402503). Based 

on the review of available toxicity data and the ECOSAR results considered in the development 

of this Problem Formulation, the aquatic risk assessment conducted for registration review will 

likely consider only the parent compound, while the approach to terrestrial risk will remain the 

same. 

Based on the various past assessments which spanned a range of application rates and patterns, 

risk tended to be greatest for freshwater fish (acute), marine/estuarine invertebrates (acute), 

birds (acute and chronic), and mammals (acute and chronic) depending on the use patterns and 

application rates. At the time of many of these assessments, certain toxicity data were not 

available [e.g. terrestrial plants, aquatic vascular plants, chronic avian, chronic invertebrates 

(freshwater and marine/estuarine) or acute marine/estuarine fish, terrestrial invertebrates] so 

risk was not assessed quantitatively or was presumed in the absence of data. A qualitative 

summary of previous risk concerns identified is provided in Table 2. 

 
Page 4 of 62

Table 2. Summary of Previous Risk Concerns Identified for Myclobutanila 

Exposure 

Basis Birds Mammals 

Terrestrial 

Plants 

Terr. 

Inverts. 

(honey 

bee 

hazard) 

Fish Aquatic 

Inverts 

Aquatic 

Plants 

Ground 

Water Persistence Degradates of Concern 

Acute Yes Yes

Yesb No 

No Yesc 

Yesb No Yes Yes 

Chronic Yes Yes No No 

a. At least one LOC has been exceeded in previous assessments 

b. Based on lack of toxicity data, risks were assumed 

c. Estuarine/marine invertebrates only 

Previous Drinking Water Assessments 

The most recent drinking water assessment (DWA) for myclobutanil was conducted in 2012, 

which re-assessed the use with the highest application rate, turf (USEPA, 2012 a.). The surface 

water estimated drinking water concentrations (EDWCs) for myclobutanil were calculated using 

a Tier II model (PRZM-EXAMS) and took into account additional aerobic aquatic metabolism data 

and revised percent crop area guidance (USEPA, 2012 b.). The estimated groundwater 

concentrations of myclobutanil were calculated using PRZM-GW. The groundwater EDWCs 

were lower than the surface water EDWCs, and EFED recommended using the surface water 

EDWCs for human health (dietary) risk assessment. The maximum concentrations of 

myclobutanil in surface water were estimated to be 218 μg/L for the 1-in-10-year annual peak, 

172 μg/L for the 1-in-10-year annual average, and 117 μg/L for the 30 year annual average. The 

maximum peak concentration of myclobutanil in groundwater was estimated to be 41.5 μg/L. 

The most recent EDWCs for 1,2,4-triazole, 1,2,4-triazole alanine, and 1,2,4-triazole acetic acid 

were calculated in support of the 2006 aggregate assessment for triazole-derivative fungicides 

(USEPA, 2006 a.; USEPA, 2006 b.). The highest 1,2,4-triazole, 1,2,4-triazole alanine, and 1,2,4-

triazole acetic acid EDWCs calculated in this assessment were for the myclobutanil turf use, 

which resulted in the surface water EDWCs (using PRZM-EXAMS) shown in Table 3. A 

groundwater EDWC of 1.06 μg/L was calculated for 1,2,4-triazole using SCI-GROW. More details 

on the methods and assumptions used to calculate these EDWCs may be found in the aggregate 

assessment. 

Table 3. Surface Water EDWCs for 1,2,4-Triazole and its Conjugates of Concern from Use of 

Myclobutanil on Turfa

 (D320682) 

Myclobutanil 

Degradate 

Estimated Surface Water Drinking Water Concentrations (μg/L) 

1-in-10-year 

annual peak 

1-in-10-year 

annual mean 

36-year 

annual mean 

1,2,4-Triazolea 41.0 11.0 2.69 

1,2,4-Triazole Acetic 

Acid (TAA) b 75.4 20.2 4.95 

1,2,4-Triazole Alanine 

(TA) c 92.7 24.9 6.08 
Page 5 of 62

a

 Golf Course Turf PA golf course turf scenario; application rate based upon 6 applications of myclobutanil 

at 1.73 lb a.i./A; 10.38 lb a.i./A/yr. 1,2,4-Triazole application was obtained from molecular weight 

conversion times myclobutanil application rate times max percent formation rate for triadimefon (turf = 

(69.0/288.78)*1.73*0.307), as this was believed to be the maximum percent formation rate for all 

fungicides in the conazole class. 

b

 TAA = (127.10/69.0)*1,2,4-Triazole concentration. 

c

 TA = (156.15/69.0)*1,2,4-Triazole concentration. 

Clean Water Act Programs 

Myclobutanil is not identified as a cause of impairment for any water bodies listed as impaired 

under section 303(d) of the Clean Water Act. Total Maximum Daily Load (TMDL) criteria have 

not been developed for myclobutanil 

(http://iaspub.epa.gov/tmdl_waters10/attains_impaired_waters.tmdls?p_pollutant_group_id=8

85). Aquatic benchmarks have been established for myclobutanil for freshwater fish (acute 

1,200 μg/L, chronic 980 μg/L), freshwater invertebrates (acute 5,500 μg/L), and freshwater 

nonvascular plants (acute 830 μg/L) 

(http://www.epa.gov/oppefed1/ecorisk_ders/aquatic_life_benchmark.htm). Any data 

submitted or otherwise located as part of the registration review process may be used to revise 

or establish new aquatic life benchmarks, if applicable. 

1. ENVIRONMENTAL FATE AND TRANSPORT 

Physical and Chemical Properties of Myclobutanil 

Selected physicochemical properties of myclobutanil are shown in Table 4. Based on these 

properties alone, volatility is not expected to be a major dissipation pathway for myclobutanil, 

and myclobutanil is not expected to bioaccumulate. 

Table 4. Selected Physical/Chemical Parameters of Myclobutanil 

Chemical name Property Data Source 

(MRID) 

Molecular weight 288.775 g/mol - 

Aqueous Solubility 

142 mg/L at 25°C 00141683

48951203 

Milli-RO Water: 118 mg/L at 20°C 

pH 4.0 buffer: 115 mg/L at 20°C 

pH 7.0 buffer: 107 mg/L at 20°C 

pH 9.0 buffer: 115 mg/L at 20°C 

46802501 

Vapor Pressure 1.60 × 10-6 torr at 25°C 48951203 

< 9.75 × 10-6 torr at 25°C 46802501 

Henry’s Law Constant 3.25 x 10-09 atm m3

/mole at 25°C Calculated 

Octanol-water partition 

coefficient (log Kow) 

2.47 at 22°C 00162541 

2.84-2.98 at unspecified ambient temperature

Mean: 2.94 00141683 
Page 6 of 62

Environmental Fate and Transport of Myclobutanil

Table 5 summarizes the environmental fate properties of myclobutanil, while Appendix A

provides the chemical structure of myclobutanil and its major degradation product, 1,2,4-

triazole. Due to its persistence and mobility, myclobutanil applications may lead to surface 

water contamination through spray drift, runoff, sediment erosion and groundwater 

contamination through leaching. Myclobutanil has been detected in rain in several agricultural 

watersheds in California (Vogel et al. 2008); thus, there is also a potential for atmospheric 

transport. 

Myclobutanil degrades rapidly as a result of aqueous photolysis (4 day half-life) and is relatively 

stable to soil photolysis (144 day half-life). Myclobutanil is stable to hydrolysis. The only aerobic 

soil metabolism study available for myclobutanil indicates that the pesticide undergoes nonlinear microbial degradation in aerobic soil, with a Double First-Order in Parallel (DFOP) half-life 

of 750 days. Myclobutanil appears to slowly degrade in a linear fashion in aerobic aquatic 

environments (half-lives of 416 and 834) and is very persistent anaerobic aquatic environments. 

The wide range of half-lives in terrestrial field studies indicates that myclobutanil may dissipate 

rapidly or slowly depending on the environmental conditions. 

Myclobutanil has the potential to leach into groundwater, as it is classified as moderately mobile 

(Kfoc = 226 – 923) (FAO 2000). A leaching study conducted on one soil suggests that myclobutanil 

residues will remain primarily in the top 10 cm of soil, although residues were found at the 20 

inch (maximum) depth and in leachate (MRID 00141681). The adsorption/desorption study 

results indicate that soil sorption of myclobutanil is highly influenced by soil acidity and soil 

cation exchange capacity. A regression analysis indicated that lower soil acidity results in 

increased soil sorption of myclobutanil; an increase in the pH by 1 increases the Kf by 3 (rsquared = 0.81; p-value < 0.05). Similarly, an increase of soil cation exchange capacity of 1 

meq/100g results in an increase in the Kf of 0.7 (r-squared = 0.81; p-value < 0.05). Sorption may 

also be influenced by soil organic carbon content. The coefficient of variance is lower for the 

Kfoc’s than for the Kf’s, indicating a correlation between myclobutanil soil sorption and soil 

organic carbon content; however, a regression analysis of percent organic carbon versus Kf for 

the five soils did not find this relationship to be statistically significant. 

Table 5. Chemical Properties and Environmental Fate Parameters of Myclobutanil 

Parameter Value* Description Source 

(MRID) Study Status 

Persistence 

Hydrolysis halflife Stable pH 5, 7, 9 at 

22 ± 2.3°C 00141679 Acceptable 

Aqueous 

photolysis halflife 4 days

(IORE) Study conducted at 31°C 

00164560

40641501 

40319801

40528801

Studies acceptable only in 

combination, not individually 
Page 7 of 62

Parameter Value* Description Source 

(MRID) Study Status 

Soil photolysis 

half-life 

144 

days 

(SFO) 

Lawrenceville silt loam 

pH 5.3 at 34°C 

00164987

00164988

Studies acceptable only in 

combination, not individually 

Aerobic soil 

metabolism halflife 

750 

days 

(DFOP)

Lawrenceville silt loam 

pH 5.3 

00141680

00164561 Individual study acceptable 

Anaerobic soil 

metabolism halflife Stable

Lawrenceville silt loam flooded 

after 30 days under aerobic 

conditions 

Flood water not characterized 

00141680

00164561 Individual study acceptable 

Aerobic aquatic 

metabolism halflife 

(total system) 

Rhine 

River 

416 

days 

(SFO) 

Pond 

834 

days 

(SFO) 

Rhine River 

pH 7.36-8.53 

at 17.1°C 

Pond 

pH 7.46-8.40 

at 12.8°C

47454401 Acceptable 

Mobility 

Adsorption– Kf 4.47 

1

/n = 

0.89 

Hagerstown Clay Loam: 1.98% OC, 

soil pH 6.4, CEC 9.4 meq/100g 

00141682 Supplemental 

1.46 

1

/n = 

0.89 

Lakeland Agricultural Sand: 0.55% 

OC, soil pH 5, CEC 1.7 meq/100g 

7.10 

1

/n = 

0.88 

Lawrenceville Silty Loam: 1.19% 

OC, soil pH 6.1, CEC 11.9 

meq/100g 

9.81 

1

/n = 

0.85 

Pasquotank Sandy Loam: 1.68% 

OC, soil pH 7.2, CEC 12.5 

meq/100g 

2.40 

1

/n = 

0.91 

Cecil Clay: 0.26% OC, soil pH 4.7, 

CEC 6.9 meq/100g 

5.05 

MEAN 

Study conducted at “ambient” 

temperature 

Adsorption– Kfoc 226 Hagerstown Clay Loam: 1.98% OC, 

soil pH 6.4, CEC 9.4 meq/100g 

266 Lakeland Agricultural Sand: 0.55% 

OC, soil pH 5, CEC 1.7 meq/100g 
Page 8 of 62

Parameter Value* Description Source 

(MRID) Study Status 

596 

Lawrenceville Silty Loam: 1.19% 

OC, soil pH 6.1, CEC 11.9 

meq/100g 

584 

Pasquotank Sandy Loam: 1.68% 

OC, soil pH 7.2, CEC 12.5 

meq/100g 

923 Cecil Clay: 0.26% OC, soil pH 4.7, 

CEC 6.9 meq/100g 

519.04

MEAN 

Study conducted at “ambient” 

temperature 

Field Dissipation 

Terrestrial Field 

Dissipation HalfLife 9.36 

days 

(IORE)

Winter wheat - Newtown, 

Pennsylvania Silty Loam, 0-3” 

depth (leached to deepest 

sampling depth of 6-12”) 

00164563

00164987

Acceptable 

80.7 

days 

(SFO) 

Winter wheat - Cleveland, 

Mississippi Loam, 0-3” depth 

(leached to deepest sampling 

depth of 6-12”) 

409 

days 

(SFO) 

Bare ground - Fresno County, 

California Sandy Loam (leached to 

deepest sampling depth of 18-

24”) 

42181101 Acceptable 

243 

days 

(IORE)

Bare ground - Santa Clara County, 

California Loam (leached to 

deepest sampling depth of 18-

24”) 

 81.6 

days**

(DFOP)

Turf – Baptistown, New Jersey Silt 

Loam (leached to deepest 

sampling depth of 18-24”) 

43087904 Supplemental 

*All values have been re-estimated by the authors of this document. Representative half-lives are 

estimated SFO half-lives (for EFED modeling inputs) from a degradation curve that does not necessarily

follow the SFO equation. Representative half-life values were calculated using nonlinear regression and 

SFO, DFOP, or IORE equations. The equations can be found in the document, Standard Operating 

Procedure for Using the NAFTA Guidance to Calculate Representative Half-life Values and Characterizing 

Pesticide Degradation (US EPA 2012). Representative half-life values calculated in this table do not include 

unextracted residues. 

**Representative half-life calculated from post-treatment day 10 to the end of the study, as maximum 

myclobutanil concentrations were observed on day 10. 
Page 9 of 62

Transformation Products 

Myclobutanil degrades to 1,2,4-triazole when subjected to light in aquatic environments or 

exposed to microbes in aerobic soil. In the aqueous photolysis study, 1,2,4-triazole comprised 

49% of the applied radioactivity on day 30 of the study. In the aerobic soil metabolism study, 

1,2,4-triazole comprised 18% of the applied radioactivity on days 150 and 180 of the study, 

declining to 13% at the end of the study (day 367). 1,2,4-triazole was observed at all depths in 

the terrestrial field dissipation studies and its formation ranged from 2.1% (6-12” segment) to 

58.6% (3-6” segment). 1,2,4-triazole is the only major transformation product of myclobutanil 

observed in field and laboratory studies; however, the analytical methods used in those studies 

are rarely able to identify 1,2,4-triazole conjugate residues separately from 1,2,4-triazole. 

Appendix A provides additional detail on degradation of myclobutanil to 1,2,4-triazole in the 

environment, including degradate and conjugate structures. 

Based on registrant-submitted laboratory and field studies, 1,2,4-triazole is persistent (average 

aerobic half-life = 645 days) and very mobile (Kf’s 0.23 – 0.84) in the soil. 1,2,4-triazole’s major

routes of dissipation are leaching into groundwater and runoff into surface water. 

Hydrolysis, aqueous photolysis, and soil metabolism are not major routes of 1,2,4-triazole 

degradation (hydrolysis half-lives 99 - 421 days; stable to aqueous photolysis). Microbial 

degradation of 1,2,4-triazole in aerobic soils is highly varied (half-lives from 20 days to stable) 

and consistently non-linear. The high variability in the half-lives may be explained, in part, by 

the application rate used in the aerobic soil metabolism studies; higher levels of application (1 to 

50 ppm in soil) seem to suppress microbial degradation. On average, even with this variability, 

1,2,4-triazole is persistent in aerobic soil. The average aerobic soil metabolism half-life for 

treatment levels at or less than 1 ppm is 197 days, while the average half-life incorporating 

treatment levels up to 50 ppm is 645 days. 1,2,4-triazole is moderately persistent in anaerobic 

soil (half-life 81 days). 

1,2,4-triazole’s major transformation products are the conjugate 1,2,4-triazole acetic acid and 

hydroxytriazole. Both transformation products are formed through microbial degradation in 

aerobic soils. In one aerobic soil metabolism study 1,2,4-triazole acetic acid comprised a 

maximum of 18% of the applied radioactivity (day 98), declining to 11.7% by the end of the 

study (day 293). In a separate aerobic soil metabolism study, hydroxytriazole comprised a 

maximum of 30.8% of the applied radioactivity (day 12), declining to 0.6% at the end of the 

study (day 180). 1,2,4-triazole acetic acid is also formed through anaerobic soil metabolism, and 

was observed at 50% of applied radioactivity on the last sample day of the only anaerobic soil 

metabolism study available for 1,2,4-triazole. 1,2,4-triazole alanine was also detected as a 

minor transformation product in the anaerobic soil metabolism study. 

1,2,4-triazole has the potential to leach into groundwater, as it is classified as mobile to 

moderately mobile (Kfoc = 48 - 202) (FAO 2000). Leaching studies conducted for 1,2,4-triazole 

suggest that the compound and its transformation products are mobile in a variety of soil types, 

with radiolabelled residues leaching to the maximum soil depth considered, 30 centimeters 

(MRIDs 00133372 and 45284030). 

Field dissipation studies indicate that 1,2,4-triazole has the propensity to leach, as the 

compound was detected up to 12 inches soil depth in field plots. Adsorption/desorption study 
Page 10 of 62

results indicate that soil organic carbon content and CEC do not influence soil sorption of 1,2,4-

triazole. Although there is a statistically significant positive relationship between Kf and soil pH, 

an increase in soil pH of 1 only increases the Kf by 0.15 (r-squared = 0.76, p-value < 0.05). 

Table 6 summarizes the environmental fate properties of 1,2,4-triazole and 1,2,4-triazole acetic 

acid, while Appendix A provides additional detail on formation of 1,2,4-triazole transformation 

products in the environment, including degradate and conjugate structures. 

 
Page 11 of 62

Table 6. Chemical Properties and Environmental Fate Parameters of 1,2,4-Triazole and 

Conjugates 

Parameter Value* Description Source (MRID) Study Status 

1,2,4-Triazole 

Persistence 

Hydrolysis 

half-life 

303 days

(DFOP) pH 5 acetate buffer at 25°C 

00133373 Supplemental 421 days

(DFOP) pH 7 phosphate buffer at 25°C 

98.7 days

(SFO) pH 9 borate buffer at 25°C 

Aqueous 

photolysis 

half-life 

Stable pH 7 distilled water 

temperature not reported 45284026 Supplemental

Aerobic soil 

metabolism 

half-life 

378 days 

(DFOP) 

Les Barges (Swiss) silty loam 

1 ppm applied 

pH 7.6 at 25°C 

45284027 Supplemental

70.1 days

(IORE) 

Laacher Hof AXXa (German) sandy loam 

~0.06 ppm applied 

pH 6.9 (H2O) at 20±2°C 

45284032 Supplemental 319 days

(DFOP) 

BBA 2.2 (German) loamy sand 

~0.06 ppm applied 

pH 6.19 (H2O) at 20±2°C 

20.3 

(IORE) 

Laacher Hof A III (German) silt loam 

~0.06 ppm applied 

pH 7.88 (H2O) at 20±2°C 

Stable 

(DFOP halflife 1,530 

days) 

Standard Soil 2.2 

50 ppm applied 

pH 6.0 at 22±2°C 

45297203 Supplemental

Stable 

(DFOP halflife 1,550 

days) 

Standard Soil 2.3 

50 ppm applied 

pH 5.5 at 22±2°C 

Anaerobic 

soil 

metabolism 

half-life 

81.2 days

(SFO) 

Les Barges (Swiss) silt loam 

pH 7.31 at 20±2°C 45930701 Acceptable 

Mobility 

Adsorption 

– Kf

0.84 

1

/n = 0.90 

Alpaugh Silty Clay: 0.65% OC, soil pH 8.8, 

CEC 30.5 meq/100g 

40891501 Acceptable 0.27 

1

/n = 0.63 

Hollister Clay Loam: 1.74% OC, soil pH 6.9, 

CEC 16.9 meq/100g 

0.23 

1

/n = 0.89 

Lakeland Sand: 0.12% OC, soil pH 4.8, 

CEC 1.2 meq/100g 
Page 12 of 62

Parameter Value* Description Source (MRID) Study Status 

1,2,4-Triazole 

0.73 

1

/n = 0.92 

Lawrenceville Silty Clay Loam: 0.70% OC, soil pH 7,

CEC 6.6 meq/100g 

0.72 

1

/n = 1.02 

Pachappa Sandy Loam: 0.81% OC, soil pH 6.9, 

CEC 11.1 meq/100g 

0.56 MEAN 

Study conducted at 25±1°C 

Adsorption 

– Kfoc

129 Alpaugh Silty Clay: 0.65% OC, soil pH 8.8, 

CEC 30.5 meq/100g 

48 Hollister Clay Loam: 1.74% OC, soil pH 6.9, 

CEC 16.9 meq/100g 

202 Lakeland Sand: 0.12% OC, soil pH 4.8, 

CEC 1.2 meq/100g 

104 Lawrenceville Silty Clay Loam: 0.70% OC, soil pH 7,

CEC 6.6 meq/100g 

89 Pachappa Sandy Loam: 0.81% OC, soil pH 6.9, 

CEC 11.1 meq/100g 

114 MEAN 

Study conducted at 25±1°C 

Field Dissipation 

Terrestrial 

Field 

Dissipation 

Half-Life 

445 days

(IORE)

Newtown, Pennsylvania Silty Loam, 0-3” depth 

(leached to 6-12” segment; study sampled to 36” 

depth)

45284025 Supplemental

391 days 

(SFO)

Newtown, Pennsylvania Silty Loam, 0-3” depth 

(leached to deepest sampling depth of 6-12”) 00164564 Supplemental

525 days

(SFO)

Cleveland, Mississippi Loam, 0-3” depth 

(leached to deepest sampling depth of 6-12”)

1,2,4-Triazole Acetic Acid 

Persistence 

Aerobic soil 

metabolism 

half-life 

5.01 

days** 

(IORE) 

SP-2.1 (German) sand 

pH 5.2 at 20°C 

46017601 Pending 

Review 

6.27 

days** 

(IORE) 

SP-2.2 (German) loamy sand 

pH 5.6 at 20°C 

7.04 

days** 

(DFOP) 

SP-2.3 (German) sandy loam 

pH 6.3 at 20°C 

*All values have been re-estimated by the authors of this document. Representative half-lives are 

estimated SFO half-lives (for EFED modeling inputs) from a degradation curve that does not necessarily

follow the SFO equation. Representative half-life values were calculated using nonlinear regression and 

SFO, DFOP, or IORE equations. The equations can be found in the document, Standard Operating 

Procedure for Using the NAFTA Guidance to Calculate Representative Half-life Values and Characterizing 
Page 13 of 62

Pesticide Degradation (US EPA 2012). Representative half-life values calculated in this table do not include 

unextracted residues. 

**This aerobic soil metabolism study did not identify any conjugates or degradates of 1,2,4-Triazole Acetic 

Acid, even though transformation products formed to upwards of 75% applied radioactivity. It is possible 

that 1,2,4-Triazole Acetic Acid in combination with its conjugates of concern are persistent in aerobic soil, 

even though, based on the data in this study, 1,2,4-Triazole Acetic Acid is not persistent in aerobic soil. 

2. RECEPTORS 

Tables 7 and 8 provide a summary of the aquatic and terrestrial toxicity data, respectively, and 

the most sensitive surrogate species tested to characterize the potential acute and chronic 

ecological effects of myclobutanil. Table 9 provides information on the most sensitive toxicity 

data available for myclobutanil degradates. All available toxicity data for myclobutanil 

degradates listed in Appendix D. 

Table 7. Summary of the Most Sensitive Endpoints from Aquatic Toxicity Studies for 

Myclobutanil 

Taxonomic 

Group 

 Study 

type 

Surrogate 

Species Toxicity 

MRID 

(classification) 

Acute Toxicity 

Classification 

Freshwater 

fish 

Acute 

Bluegill Sunfish 

(Lepomis 

macrochirus) 

96-hr LC50: 2.4 mg a.i./L 

NOAEC = 1.5 mg a.i./L 

LOAEC = 2.7 mg a.i./L based on 

quiescence, loss of equilibrium 

and death. 

00144285 

(Acceptable) 

Moderately 

toxic 

Chronic 

Fathead 

minnow 

(Pimephales 

promelas) 

NOAEC= 0.98 mg a.i./L1 

LOAEC = 2.2 mg a.i./L based on 

a 9.7% reduction in body 

length. 

Total mortality at 8.5 mg a.i./L 

00164986/ 

40409201/ 

40480401 

(Acceptable) 

N/A 

Estuarine/ 

marine fish 

Acute 

Sheepshead 

minnow 

(Cyprinodon 

variegatus) 

96-hr LC50: 4.7 mg a.i./L 

NOAEC = 1.2 mg a.i./L 

LOAEC = 1.8 mg a.i./L (erratic 

behavior, darkened 

pigmentation, lethargy; fish at 

higher concentration levels 

also exhibited partial loss of 

equilibrium and rapid 

respiration). Mortality was 5% 

at 3.8 mg a.i./L and 100% at 6.3 

mg a.i./L 

42747903 

(Acceptable) 

Moderately 

toxic 

Chronic N/A No Data --- --- 

Freshwater 

invertebrates 

Acute 

Water flea 

(Daphnia 

magna) 

 48-hr EC50: 11 mg a.i./L 

NOAEC = 3.2 mg a.i./L 

LOAEC = 5.6 mg a.i./L (settled 

to the bottom). Mortality was 

45% at 10 mg a.i./L and 90% at 

18 mg a.i./L 

00141678 

(Acceptable) Slightly toxic 

Chronic 

Water flea 

(Daphnia 

magna) 

Estimated NOAEC using ACR= 

3.9 mg a.i./L2 

No Study N/A 
Page 14 of 62

Taxonomic 

Group 

 Study 

type 

Surrogate 

Species Toxicity 

MRID 

(classification) 

Acute Toxicity 

Classification 

Estuarine 

/marine 

invertebrates 

Acute 

Eastern oyster 

(Crassostrea 

virginica)

96-hr EC50: 0.68 mg a.i./L 

NOAEC = 0.48 mg a.i./L 

LOAEC = 0.78 mg a.i./L (shell 

deposition). Inadequate shell 

growth in controls may 

underestimate pesticide 

related shell growth effects. 

(Discussed in Section 4. 

Preliminary Identification of 

Data Gaps) 

42747901 

(Supplemental) Highly toxic 

Mysid shrimp 

(Americamysis 

bahia) 

96-hr LC50: 0.24 mg a.i./L 

NOAEC could not be 

determined as effects seen at 

all dose levels (erratic 

swimming behavior, darkened 

pigmentation, lethargy). 

Mortality observed at lowest 

test concentration of 0.180 mg 

a.i./L and above. 

42747902 

(Acceptable) Highly toxic 

Chronic 

Mysid shrimp 

(Americamysis 

bahia) 

NOAEC: 0.0856 mg a.i./L 

LOAEC: >0.0856 mg a.i./L 

No effects reported at any 

level. 

Water quality issues (a 

maximum pH of 9.98 was 

reported at the nominal 20 ug 

a.i./L treatment level). 

47968901 

(Supplemental) N/A 

Aquatic 

Plants Non 

vascular 

Green algae 

(Selenastrum 

capricornutum)

120-hr EC50: 0.83 mg a.i./L 

NOAEC= 0.56 mg a.i./L based 

on cell density. 

41984801 

(Acceptable) N/A 

Vascular No Data --- --- --- 

1

 Acute data for fathead minnow was requested in Table 11 below to provide data for determination of 

an ACR. 

2 Estimated from the mysid acute and chronic toxicity data and the daphnid acute data using the acute 

to chronic ratio (ACR) [0.24/0.0856 x 11/x; x=3.9] 

 
Page 15 of 62

Table 8. Summary of the Most Sensitive Endpoints from Terrestrial Toxicity Studies for 

Myclobutanil 

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) 

Acute Toxicity 

Classification 

Birds 

Acute 

Bobwhite 

quail 

(Colinus 

virginianus) 

Acute LD50: 498 mg a.i./kg-bw 

NOAEL: not determined 

LOAEL= 316 mg/kg (lethargy 

and anorexia). Mortalities at 

all dose levels (1, 4, 8, 10 and 

10, respectively). Good dose 

response. 

00144286 

(Acceptable) Slightly toxic 

Subacute 

Mallard 

(Anas 

platyrhync

hos) 

Subacute dietary LC50 >4090 

mg a.i./kg-diet 

NOAEC= 1250 mg a.i./kg-diet 

LOAEC= 2220 mg a.i./kg-diet 

(anorexia and lethargy). One 

bird died at 4090 mg a.i./kgdiet. 

00144288 

(Acceptable) Slightly toxic 

Chronic 

Bobwhite 

quail 

(Colinus 

virginianus) 

NOAEC= 256 mg a.i./kg-diet 

LOAEC >256 mg a.i./kg-diet 

No treatment-related effects 

at any level. Maximum 

exposure levels less than the 

predicted EECs. 

43087901 

(Supplemental) N/A 

Mammals1 

Acute 

Laboratory 

mouse 

(Mus 

musculus) 

LD50= 1360 mg a.i./kg bw 

Mortality at all dose levels 

tested. Multiple clinical signs, 

including ataxia, tremors, loss 

of righting and others – not 

dose-related; however, early 

deaths may have affected 

reporting. 

00165239 

(Acceptable) Slightly toxic 

Acute 

Laboratory 

rat (Rattus 

norvegicus) LD50= 1600 mg a.i./kg bw (M) 00141662 

(Acceptable) Slightly toxic 

Chronic 

Laboratory 

rat 

(Rattus 

norvegicus) 

NOAEC (NOAEL)= 200 mg 

a.i./kg-diet (16 mg/kg 

bw/day) 

LOAEC (LOAEL)=1000 mg 

a.i./kg-diet (80 mg/kg bw/day) 

-testicular, epididymal and 

prostatic atrophy in P2 males; 

slight increase in stillborns, 

decrease in body weight gain 

00149581/ 

00143766 

(Acceptable) 

N/A 
Page 16 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) 

Acute Toxicity 

Classification 

in pups during lactation in F1 

and F2 generations 

Terrestrial 

Invertebrat

es 

Acute 

Honey bee 

(Apis 

mellifera 

L.) 

Contact LD50 

> 100 μg a.i./bee 

00144289 

(Acceptable) N/A 

1 Toxicity data for the oral mouse study was more sensitive than the rat study (oral mouse dose converts

to a rat equivalent dose of 665 mg/kg bw). Rat data was included as this endpoint was used in HED 

assessments and for comparison to degradate toxicity data where rat was more sensitive than mouse in 

acute oral study (see Table 9). 

Table 9. Summary of the Most Sensitive Data for each taxa for Myclobutanil Degradates 

(1,2,4-triazole, triazole alanine and triazole acetic acid)1 

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

1,2,4-triazole (aquatic toxicity) 

Freshwater 

fish 

Acute 

Rainbow Trout 

(Oncorhynchus 

mykiss) 

96 hr-LC50 = 498 mg 

ai/L 

NOAEC = 378 mg ai/L 

(mortality) 

48474301 

(Acceptable) None 

Chronic (28 day 

growth toxicity 

test) 

Rainbow trout 

(Oncorhynchus 

mykiss) 

LC50: > 100 mg/L 

NOAEC (growth) ≥ 

100 mg/L 

NOAEC (sublethal 

effects) = 3.2 mg/L 

LOAEC (sublethal 

effects) = 10.0 mg/L 

Observed sublethal 

effects included 

multiple fish being 

inactive or displaying 

abnormally low 

activity, labored 

respiration, and lying 

inactive on the 

bottom of the 

aquarium in the 

three highest 

45880405 

(Supplemental) 

Supplemental due to 

non-guideline study 
Page 17 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

concentrations 

tested between days 

23 and 

28. 

Freshwater 

Invertebrat

es 

Acute 

Water flea 

(Daphnia 

magna) 

 LC50 = 900 (730 to 

2200, 95% C.I.) mg/L. 00133381 Under Review 

Acute 

Water flea 

(Daphnia 

magna)

48-hr EC50 > 98.1 mg 

ai/L 

NOAEC = 98.1 mg 

ai/L (based on 

mobility, highest 

concentration tested) 

48453206 

(Acceptable) None 

Aquatic 

Plants - 

Non 

vascular 

Acute 

Freshwater 

Algae 

(Pseudokirchn

eriella 

subcapitata, 

formerly 

Selenastrum 

capricornutum

)

96-hr endpoints: 

Biomass (most 

sensitive): 

EC50 = 14 mg ai/L 

NOAEC = 3.1 mg ai/L 

Cell Density: 

EC50 = 18 mg ai/L 

NOAEC = 6.8 mg ai/L 

Growth Rate: 

EC50 > 31 mg ai/L 

NOAEC = 6.8 mg ai/L 

45880401 

(Acceptable) None

 Acute 

Green algae 

(Scenedesmus 

subspicatus) 

EC50 = 6.3 (5.5 to 7.1, 

95% C.I.) mg/L 00133382 Under Review 

1,2,4-triazole (terrestrial toxicity) 

Birds 

 Acute 

Coturnix quail 

(Coturnix 

japonica)

LD50 >316 mg/kg bw 45284015 Under Review

 Acute 

Bobwhite quail 

(Colinus 

virginianus) 

LD50 = 770 mg/kg bw 

NOAEL = 245 mg/kg 

bw 

LOAEL = 392 based 

on reduced body 

weight and food 

consumption; other 

observed effects 

included mortality 

49380701 

(Acceptable) None 
Page 18 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

and clinical signs of 

toxicity 

Mammals 

Acute 

Laboratory 

mouse (Mus 

musculus)

LD50 = 3650 mg/kg 45284001 Review not available2 

Acute 

Laboratory Rat 

(M) 

(Rattus 

norvegicus)

LD50 = 1375 mg/kg 

LD50 = 1648-3080 

mg/kg 

45284008 

45284004, 

45284001 

Reviews not 

available2

Reproduction 

and fertility 

effects

0, 250, 500, 

3000 ppm 

M: 15, 31, 189 

mkd 

F: 18, 36, 218 

mkd 

Laboratory rat 

(Rattus 

norvegicus)

Parental: 

NOAEC/NOAEL <250 

ppm/15 mg/kg/day 

LOAEC/LOAEL= 250 

ppm/15 mg/kg/day 

based on decrease in 

bodyweight, 

bodyweight gain and 

spleen weight. 

Offspring: 

NOAEC/NOAEL= 

<250 ppm/19 

mg/kg/day 

LOAEC/LOAEL= 250 

ppm/19 mg/kg/day 

based on decrease in 

bodyweight, 

bodyweight gain, 

brain and spleen 

weights 

Reproduction: 

NOAEC/NOAEL= 250 

ppm/15 mg/kg/day 

Repro LOAEC/LOAEL= 

500 ppm/31 

mg/kg/day based on 

abnormal sperm and 

↓# of corpus luteum 

(CL) in F1 females 

At 3000 ppm/218 

mg/kg/day, 

reproductive failure 

(no viable offspring), 

↑CL in F0 parental 

females

46467304 

(Acceptable) None 
Page 19 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

Developmental 

Toxicity in 

Rabbits 

0,5,15,30,45 

mg/kg/day 

New Zealand 

white rabbit 

Parental/ 

Developmental: 

NOAEL= 30 

mg/kg/day 

LOAEL= 45 

mg/kg/day based on 

mortality and clinical 

signs (decreased 

motor activity, head 

tilt, lacrimation, 

drooping eyelids, 

diarrhea and 

salivation) for 

parental effects and 

decreased fetal 

weight and urinary 

tract malformations 

for developmental 

effects 

Mortality (6/25 

rabbits) in 45 

mg/kg/day group 

46492903 

(Acceptable) None 

Terrestrial 

Invertebrat

es 

Acute and 

reproductive (28 

days) 

Collembolan 

(springtails) 

Species 

(Folsomia 

candida) soil 

arthropods 

LC50>10 mg/kg 

NOAEC (mortality) ≥ 

10mg/kg 

NOAEC 

(reproduction) = 1.8 

mg/kg 

45880404 

(Supplemental) Non-guideline study 

Growth and 

reproductive (8 

weeks, adult 28 

day exposure, 

additional 4 

week offspring 

exposure) 

Earthworms 

(Eisenia fetida)

LC50> 70.81 ug/kg 

NOAEC ≥ 70.81 ug/kg 

(highest 

concentration tested)

No significant 

treatment effects for 

mortality, behavior, 

body weights, 

reproduction or food 

consumption 

45880402 

(Supplemental) Non-guideline study 

Triazole alanine (aquatic toxicity) 

No submitted data identified 

Triazole alanine (terrestrial toxicity) 
Page 20 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

Mammals 

90-day oral 

toxicity in 

rodents – rat 

0, 1250, 5000, 

20000 ppm 

M: 0, 90, 370, 

1510 mg/kg/day 

F: 0,160, 400, 

1680 mg/kg/day 

Laboratory rat 

(Rattus 

norvegicus)

NOAEL = 90/160 

mg/kg/day (M/F) 

LOAEL = 370/400 

mg/kg/day (M/F) 

based on decreased 

leukocyte counts and 

decreased 

triglycerides in 

females 

At 1510/1680 

mg/kg/day (M/F) 

decreased body 

weight (M), body 

weight gain (M), 

leukocytes (M/F) and 

triglycerides (M/F) 

00164107 

(Acceptable) None 

Reproduction 

and fertility 

effects

0, 200, 2000, 

10000 ppm 

M: (F0/F1) 0, 

50/47, 213/192, 

1098/929 

mg/kg/day 

F: 0, 51/49, 

223/199, 

1109/988 

mg/kg/day 

Laboratory rat 

(Rattus 

norvegicus)

Parental: 

NOAEC/NOAEL= 

10000 ppm/929 

mg/kg/day 

LOAEC/LOAEL: 

>10000 

ppm/929mg/kg/day 

Offspring: 

NOAEC/NOAEL <250 

ppm/19 mg/kg/day 

LOAEC/LOAEL=2000p

pm/192 mg/kg/day 

based on reduced 

mean litter weights 

in both generations 

Reproduction: 

LOAEC/LOAEL>10000 

ppm/929mg/kg/day

00164112 

(Acceptable) None 

Triazole acetic acid (aquatic toxicity) 

Freshwater 

Fish Acute 

Rainbow trout 

(Oncorhynchus 

mykiss) 

96 hr-LC50 >101 mg 

ai/L 

NOAEC = 101 mg ai/L 

(mortality/sub-lethal 

effects) 

48453209 

(Acceptable) None 

Freshwater 

Invertebrat

es 

Acute 

Water flea 

(Daphnia 

magna)

48-hr EC50 > 108 mg 

ai/L 

NOAEC = 108 mg ai/L 

48453208 

(Acceptable) None 
Page 21 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

(based on mobility, 

highest 

concentration tested) 

Triazole acetic acid (terrestrial toxicity)

Mammals 

Acute 

Laboratory rat 

(Rattus 

norvegicus)

LD50 > 5000 mg/kg 45596802 Review not available2

14 day oral 

toxicity in 

rodents 

0, 100, 1000, 

8000 ppm 

M: 0, 10.6, 

102.8, 788.3 

mg/kg/day 

F: 0, 10.1, 97.2, 

703.5 

mg/kg/day 

Laboratory rat 

(Rattus 

norvegicus)

NOAEL = 788.3/703.5 

mg/kg/day 

(M/F) 

LOAEL >788.3/>703.5 

mg/kg/day (M/F) 

45596801 None 

1 Many endpoints derived from summary document USEPA 2006 b. 1,2,4-Triazole, Triazole 

Alanine, Triazole Acetic Acid: Human Health Aggregate Risk Assessment in Support of 

Reregistration and Registration Actions for Triazole-derivative Fungicide Compounds. 

2 Values taken from triazole aggregate study referenced above, where it was noted that some 

values were from submitted summary data and full study reports were not available. 

 

Exposure Pathways of Concern 

The exposure pathways for myclobutanil and its transformation products may result in a wide 

range of potential aquatic and terrestrial exposure scenarios. For this problem formulation, the 

drinking water and inhalation pathways for birds and mammals were screened using the SIP 

(Screening Imbibition Program) and STIR (Screening Tool for Inhalation Risk) screening methods. 

STIR found the inhalation pathway not likely to be significant but the SIP analysis identified 

exposure through drinking water alone to be a potential concern for birds (acute and chronic) 

and mammals (chronic only). This is primarily due to the high water solubility of the compound 

and is a route of exposure that will be further analyzed in the forthcoming risk assessment. 

It is also noted that these screening analyses do not include aggregation with all other exposure 

pathways (dietary, dermal, inhalation, or drinking water), which, together, may contribute to a 

total exposure that has a potential for effects to non-target animals. The risk characterization 

section will discusses the impact of the consideration of other routes of exposure that have 
Page 22 of 62

been identified as potentially important, and the degree of certainty associated with screeninglevel risk assessment conclusions. SIP and STIR are described in detail at 

http://www.epa.gov/oppefed1/models/terrestrial/index.htm and the SIP and STIR model inputs 

and outputs for myclobutanil are available in Appendices B and C, respectively. 

 

3. ANALYSIS PLAN 

Drinking Water Assessment 

An updated drinking water assessment will be conducted to support future human health 

dietary risk assessments of myclobutanil, as well as an updated aggregate drinking water 

assessment for triazole-derivative fungicides. Such an assessment is needed because the fate 

half-lives calculated for this problem formulation in accordance with recent guidance (USEPA 

2012 c.,d.) are likely to alter drinking water exposure estimates. The drinking water assessment 

will incorporate model estimates of myclobutanil and any additional transformation products to 

those previously identified by the Health Effects Division as residues of toxicological concern in 

surface water and groundwater. The registration review drinking water assessment will include 

modeling results as well as a summary of available surface water and groundwater monitoring 

data, if available. 

The current model for conducting drinking water assessments for surface water is the Surface 

Water Concentration Calculator (SWCC). In the absence of newer models approved within OPP, 

it is expected that SWCC will be used to simulate pesticide transport as a result of runoff and 

erosion from an agricultural field and to estimate environmental fate and transport of pesticides 

in the index reservoir. Measures of exposure will be based on maximum single and year 

(including multiple seasons per year) labeled application rates, minimum retreatment intervals, 

and conservative methods of application. 

Currently, groundwater modeling is completed using PRZM-Groundwater (PRZM-GW). PRZMGW is used to simulate vertical pesticide transport through the soil profile into an aquifer 

following application to an agricultural field. The PRZM scenarios used in groundwater 

simulations are representative of vulnerable sites—shallow unconfined aquifers under an 

agricultural field with leaching prone soil—and output values represent pesticide concentrations 

that may be observed in drinking water resulting from the use of groundwater vulnerable to 

pesticide contamination as source water. The results are expected to represent the upper bound 

values on the concentrations of toxic residues that might be found in drinking water supplied by 

groundwater. 

Ecological Risk Assessment 

Stressors of Concern 

Toxicity data for the primary degradate of concern 1,2,4-triazole as well as its conjugates (1,2,4-

triazole alanine and 1,2,4-triazole acetic acid) are presented in Table 6. Only the 1,2,4-triazole 

degradate was considered a major degradate based on soil and water metabolism studies for 

myclobutanil; however, 1,2,4-triazole acetic acid was a major degradate in fate studies 

conducted for 1,2,4-triazole, and there is evidence that 1,2,4-triazole and the triazole conjugates 

can interconvert in soil and aquatic systems. (USEPA, 2006 a.). In addition to environmental 
Page 23 of 62

degradates of concern, plant and mammalian metabolites of concern of myclobutanil include 

1,2,4-triazole, 1,2,4-triazole alanine, 1,2,4-triazole acetic acid and RH-9090 [α-(3-hydroxybutyl)-

α-(4-chlorophenyl)-1H-1,2,4-triazole-1-propanenitrile]. In addition to 1,2,4-triazole acetic acid, 

hydroxytriazole was identified as a major transformation product of 1,2,4-triazole. Based on 

myclobutanil’s persistence in soil and water, it is considered unlikely that hydroxytriazole will 

reach levels greater than 10% of the parent compound in the environment. No toxicity data 

were available for hydroxytriazole. 

Based on review of toxicity studies available for 1,2,4-triazole, 1,2,4- triazole alanine and 1,2,4-

triazole acetic acid, these degradates appear to generally show similar or less toxicity to aquatic 

or terrestrial organisms than the parent compound, myclobutanil. In general, aquatic species 

appear to be less sensitive to the degradates, whereas birds and mammals tend to show similar 

toxicity. Previous documents (USEPA, 2006 b., Duah, et al. 2001) referenced an oral rabbit study 

with an LD50 of 666 mg/kg/day for 1,2,4-triazole but the study results could not be substantiated 

with the available literature (MRID cited did not contain an oral rabbit study). There has been 

some concern raised in other discussions (USEPA 2006 b., Duah, et al. 2001) about the possible 

increased sensitivity of rabbits to the triazole degradates based on the reported oral LD50 of 666 

mg/kg/day and mortality seen at 45 mg/kg/day in the neurodevelopmental study (MRID 

46492903). 

Although no toxicity studies are available for the metabolite RH-9090, this compound is 

considered to be of equivalent toxicity to the parent based on the structural activity relationship 

(SAR) (USEPA, 2006 b.). In addition, tolerances for myclobutanil residues in food are established 

for the combined residues of myclobutanil and RH-9090 on registered commodities. For the 

degradates of concern, ECOSAR (Ecological Structure Activity Relationship), v1.11, and SMILES 

Codes were used to assess their toxicity relative to the parent compound myclobutanil and 

aquatic organisms. Predicted values from ECOSAR for the parent compound myclobutanil were 

generally in agreement with the toxicity study results, indicating ECOSAR may be useful for 

estimating degradate toxicity. The ECOSAR analysis indicated lower predicted toxicity for each of 

the degradation products than the parent, including the degradate hydroxytriazole, for which no 

toxicity data were available. Results of this analysis as well as a summary table comparing 

toxicity study endpoints for myclobutanil and its degradates are included in Appendix D. 

Previous assessments have used a Total Toxic Residue (TTR) approach for assessing ecological 

and drinking water risks for myclobutanil and residues of concern in the absence of empirical 

toxicity data for the degradates. This modeling strategy uses the assumption that all residues of 

concern have similar physical, chemical, and partitioning characteristics as well as equal or less 

toxicity than the parent compound. Based on the review of the toxicity studies available on the 

degradation products and ECOSAR analysis, it is anticipated that the TTR approach will not be 

necessary for the aquatic ecological assessment and only the parent compound will be 

considered due to the lower toxicity of the degradates compared to the parent. However, as 

myclobutanil and its transformation products of concern have generally equivalent toxicity for 

birds and mammals, degradates would be considered as part of the terrestrial assessment for 

these species by using a conservative foliar half-life for the terrestrial analysis. 

Measures of Exposure
Page 24 of 62

In order to estimate risks of myclobutanil exposure to aquatic and terrestrial organisms, all 

exposure modeling and resulting risk conclusions will be made based on maximum application 

rates, application methods, and any mitigation measures specifically indicated on the label. The 

models that will be used to predict the estimated environmental concentrations (EECs) of 

myclobutanil are discussed on OPP’s model website 

http://www.epa.gov/opp00001/science/models_pg.htm. In addition, E-FAST and any additional 

available exposure models may be used to assess use in drains, drain lines, irrigation supply 

systems, waste water systems, sewage systems, sewer lines, and storm sewers. E-FAST is 

described in detail at http://www.epa.gov/oppt/exposure/pubs/efast.htm.

The registration review preliminary risk assessment may include modeling exposures for some 

crops to account for the multiple crop cycles or crop rotations that may occur within a given 

calendar year which may not have been previously considered. 

The Agency is also aware of monitoring conducted by federal and state agencies and this route 

of exposure will be considered in the assessment to the extent that data on myclobutanil and 

1,2,4-triazole are available. 

Measure of Effects 

Ecological effects data are used as measures of direct and indirect effects to biological 

receptors. Data are typically obtained from registrant-submitted studies and from literature 

studies identified by ECOTOX. The ECOTOX database provides more ecological effects data in an 

attempt to bridge existing data gaps. ECOTOX is a source for locating single chemical toxicity 

data and potential chemical mixture toxicity data for aquatic life, terrestrial plants, and 

wildlife. ECOTOX was created and is maintained by the U.S. EPA, Office of Research and 

Development, and the National Health and Environmental Effects Research Laboratory's MidContinent Ecology Division. Deficiencies were identified in the available toxicology data 

submitted to date from the registrant, including data gaps based on new guidelines or concern 

about species sensitivities. These are outlined in Tables 11 and 12 below. 

Integration of Exposure and Effects 

Risk characterization is the integration of exposure and ecological effects to determine the 

potential ecological risk from the use of pesticides and the likelihood of direct and indirect 

effects to non-target organisms in aquatic and terrestrial habitats. For the assessment of risks, 

the risk quotient (RQ) method is used to compare exposure and measured toxicity values. EECs 

are calculated for acute and chronic concentrations and are compared to acute and chronic 

toxicity endpoints. The resulting RQs are then compared to the Agency’s Levels of Concern 

(LOCs) (USEPA 2004). These criteria will be used to indicate when myclobutanil use, as directed 

on the label, has the potential to cause adverse direct effects to non-target organisms. In 

addition, any available incident data will be considered (see below) as part of the risk 

characterization.

Endangered Species Assessments 

In November 2013, the EPA, along with the U.S. Fish & Wildlife Service (USFWS), the National 

Marine Fisheries Service (NMFS) (collectively, the Services), and the U.S. Department of 
Page 25 of 62

Agriculture (USDA) released a summary of their joint Interim Approaches for assessing risks to 

listed species from pesticides. The Interim Approaches were developed jointly by the agencies in 

response to the National Academy of Sciences’ (NAS) recommendations and reflect a common 

approach to risk assessment shared by the agencies as a way of addressing scientific differences 

between the EPA and the Services. The NAS report outlines recommendations on specific 

scientific and technical issues related to the development of pesticide risk assessments that EPA 

and the Services must conduct in connection with their obligations under the Endangered 

Species Act (ESA) and FIFRA. The joint Interim Approaches were released prior to a stakeholder 

workshop held on November 15, 2013. In addition, the EPA presented the joint Interim 

Approaches at the December 2013 Pesticide Program Dialogue Committee (PPDC) and StateFIFRA Issues Research and Evaluation Group (SFIREG) meetings, and held a stakeholder 

workshop in April 2014, allowing additional opportunities for stakeholders to comment on the 

Interim Approaches. As part of a phased, iterative process for developing the Interim 

Approaches, the agencies will also consider public comments on the Interim Approaches in 

connection with the development of upcoming Registration Review decisions. The details of the 

joint Interim Approaches are contained in the white paper “Interim Approaches for NationalLevel Pesticide Endangered Species Act Assessments Based on the Recommendations of the 

National Academy of Sciences April 2013 Report,” dated November 1, 2013. 

Given that the agencies are continuing to develop and work toward implementation of the 

Interim Approaches to assess the potential risks of pesticides to listed species and their 

designated critical habitat, the ecological risk assessment supporting the proposed interim 

registration review decision for myclobutanil is not expected to contain a complete ESA analysis. 

Once the agencies have fully vetted the scientific methods necessary to complete risk 

assessments for endangered and threatened (listed) species and their designated critical 

habitats, these methods will be applied to subsequent analyses for myclobutanil as part of 

completing this registration review. 

Endocrine Disruptor Screening Program 

As required by FIFRA and FFDCA, EPA reviews numerous studies to assess potential adverse 

outcomes from exposure to chemicals. Collectively, these studies include acute, subchronic and 

chronic toxicity, including assessments of carcinogenicity, neurotoxicity, developmental, 

reproductive, and general or systemic toxicity. These studies include endpoints which may be 

susceptible to endocrine influence, including effects on endocrine target organ histopathology, 

organ weights, estrus cyclicity, sexual maturation, fertility, pregnancy rates, reproductive loss, 

and sex ratios in offspring. For ecological hazard assessments, EPA evaluates acute tests and 

chronic studies that assess growth, developmental and reproductive effects in different 

taxonomic groups. As part of registration review for myclobutanil, EPA will review these data 

and select the most sensitive endpoints for relevant risk assessment scenarios from the existing 

hazard database. However, as required by FFDCA section 408(p), myclobutanil is subject to the 

endocrine screening part of the Endocrine Disruptor Screening Program (EDSP). 

EPA has developed the EDSP to determine whether certain substances (including pesticide 

active and other ingredients) may have an effect in humans or wildlife similar to an effect 

produced by a “naturally occurring estrogen, or other such endocrine effects as the 

Administrator may designate.” The EDSP employs a two-tiered approach to making the 

statutorily required determinations. Tier 1 consists of a battery of 11 screening assays to identify 
Page 26 of 62

the potential of a chemical substance to interact with the estrogen, androgen, or thyroid (E, A, 

or T) hormonal systems. Chemicals that go through Tier 1 screening and are found to have the 

potential to interact with E, A, or T hormonal systems will proceed to the next stage of the EDSP 

where EPA will determine which, if any, of the Tier 2 tests are necessary based on the available 

data. Tier 2 testing is designed to identify any adverse endocrine-related effects caused by the 

substance, and establish a dose-response relationship between the dose and the E, A, or T 

effect. 

Under FFDCA section 408(p), the Agency must screen all pesticide chemicals. Between October 

2009 and February 2010, EPA issued test orders/data call-ins for the first group of 67 chemicals, 

which contains 58 pesticide active ingredients and 9 inert ingredients. A second list of chemicals 

identified for EDSP screening was published on June 14, 2013[1] and includes some pesticides 

scheduled for registration review and chemicals found in water. Neither of these lists should be 

construed as a list of known or likely endocrine disruptors. 

Myclobutanil is on List 1 for which EPA has received all the required Tier 1 assay data. The 

Agency is currently reviewing all of the assay data received for the appropriate List 1 chemicals 

and planning to make the conclusions of those reviews available in early 2015. For further 

information on the status of the EDSP, the policies and procedures, the lists of chemicals, future 

lists, the test guidelines, and the Tier 1 screening battery, please visit our website.[2]

[1] See http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2009-0477-0074 for the 

final second list of chemicals. 

[2] http://www.epa.gov/endo/

Review of Incident Data

Three incident databases are available: 1) the Ecological Incident Information System v. 2.1.1 

(EIIS), maintained by EFED; 2) the Avian Incident Monitoring System (AIMS), maintained by the 

American Bird Conservancy; and, 3) the Incident Data System (IDS) maintained by OPP. These 

databases were searched on 11/12/14. 

The Ecological Incident Information System (EIIS) database was queried for incidents related to 

myclobutanil use. Four incidents were reported in the EIIS database, three with effects on 

terrestrial plants (two incidents with grapes and one with roses) and one on aquatic species 

(both fish and invertebrates). The two incidents with grapes occurred in California and the one 

with roses was reported in Maryland. The certainty index for the damage in all 3 incidents to 

plants was rated as possibly related to exposure to myclobutanil. The two incidents with grapes 

involved application of other pesticides as well as the myclobutanil. Therefore, it is not 

definitively known whether or not the effects were due to exposure to myclobutanil in these 

two incidents. Myclobutanil was the only pesticide applied to the rose bushes in the third plant 

reported incident. In the fourth incident involving aquatic species, the incident was rated as 

highly probable. However, one other pesticide was involved in this incident; therefore, it is not 

definitely known whether or not the effects were due to myclobutanil exposure. 

Incident 1: On May 30, 1994, Rally 40W (myclobutanil), Pro Gibb (gibberellic acid), 

dimethogan 25 WP, Pro Kil Cryolite 96 (sodium fluoaluminate), Britz binder and Booster 42 
Page 27 of 62

Foliar Spray (polymeric polyhydroxy acids) were applied by ground application to grape vines. 

Shortly after the last application, scarring of the berries, stunted vine growth, lack of berry size 

increase, dieback of fruit from total bunches and limited cone growth with straggly branches 

were observed. No residue analysis was conducted. The California Commissioner’s report 

indicated that mixtures of Pro-Gibb 4% and Pro-Kil Cryolite 96 may have caused some 

compatibility problems. No specific data on terrestrial plants were found in the Agency files for 

any of the pesticides applied on this incident. 

Incident 2: On June 2, 2000, it was reported that Rally 40W damaged 6 acres of Red 

Globe and Thompson’s grapes to the extent that they were unfit for sale. Burns and necrosis on 

bunches (Red Globe) and leaf burn (Thompson’s) were observed. Agri-MEK (abamectin) and AdWet were also applied, using a ground spray on the vineyard. No plant tissue or environmental 

samples were found in the Agency files for any of the pesticides applied in this incident. 

Incident 3: On June 16, 2003, Systhane (myclobutanil) was applied via a broadcast spray 

to rose bushes grown in greenhouses by local residents in Maryland. The total magnitude was 

200 houses. Foliar necrosis and some defoliation were observed after exposure to Systhane. 

Damage varied from house to house and by rose variety. No plant tissue or environmental 

samples were collected for this incident. 

Incident 4: On July 28, 2009, an investigator for the Iowa Department of Natural 

Resources visited a grower who was concerned an airplane may have applied or may have 

allowed a pesticide application to drift into Flint Creek in Des Moines County, IA. The inspector 

observed dead and dying crayfish in the creek. Freshwater bluegill were also found dead. The 

active ingredients chlorpyrifos and myclobutanil were detected in bluegill tissue samples. 

A query of the aggregate Incident System (IDS) on 11/12/2014 reported 29 incidents to plants 

(dates ranging from 1998-2012). 

The Avian Incident Monitoring System (AIMS), a database administered by the American Bird 

Conservancy, was queried for myclobutanil on 11/12/2014 and to date, there were no bird 

incidents reported. 

The absence of documented incidents in these databases does not necessarily mean that such 

incidents did not occur. Mortality incidents must be seen, reported, investigated, and submitted 

to the Agency in order to be recorded in the incident databases. In addition, incident reports for 

non-target organisms typically provide information only on mortality events and plant damage. 

Sublethal effects in organisms such as abnormal behavior, reduced growth and/or impaired 

reproduction are rarely reported, except for phytotoxic effects in terrestrial plants. 

Uncertainties

• As previously discussed, many of the labels do not specify the maximum number 

of applications that can be applied per year or crop cycle and/or the number of 

crop cycles per year. Some labels are missing a single maximum application rate. 

We request that in completing the Use Pattern Summary Table, the registrants 

provide this information. 

 
Page 28 of 62

4. PRELIMINARY IDENTIFICATION OF DATA GAPS 

Environmental Fate 

Table 10 identifies the environmental fate studies by MRID that offer data for each Part 158 

data requirement, as well as study classifications and whether or not further data are 

anticipated to be needed in order to support risk assessment for the myclobutanil registration 

review. Although no additional fate and transport data are being requested for myclobutanil 

under registration review, the table indicates studies for which data voluntarily submitted by the 

registrant may assist in refining the assessment. No additional data for 1,2,4-triazole or its 

conjugates are needed to conduct the myclobutanil drinking water or ecological risk 

assessments under registration review. 

Table 10. Submitted Environmental Fate Data for Myclobutanil 

OCSPP 

Guideline

Data 

Requirement 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed? Additional Comments 

835.2120 Hydrolysis 00141679 Acceptable No None

835.2240 Aqueous 

photolysis 

00164560 

40641501 

40319801 

40528801 

Acceptable in 

combination No 

Not requesting data but any 

additional studies submitted 

voluntarily would help refine the 

assessment 

835.2410 Soil photolysis 00164987 

00164988 

Acceptable in 

combination No 

None

835.4100 Aerobic soil 

metabolism 00141680 

00164561 Individual study 

acceptable No

Not requesting data but any 

additional studies submitted 

voluntarily would help refine the 

assessment 

835.4200 Anaerobic soil 

metabolism 00141680 

00164561 

Individual study 

acceptable No 

Not requesting data but any 

additional studies submitted 

voluntarily would help refine the 

assessment 

835.4300 Aerobic aquatic 

metabolism 47454401 Acceptable No None

835.4400 Anaerobic 

aquatic 

metabolism No data No 

Not requesting data but any 

additional studies submitted 

voluntarily would help refine the 

assessment 

835.1230 Adsorption/ 

desorption 00141682 Supplemental No None

835.1410 Volatility –

laboratory No data No 

Not triggered based on low 

vapor pressure (7.07X10-9 torr at 

25°C) 

835.6100 Terrestrial field 

dissipation 

00164563 

00164987 Acceptable No None
Page 29 of 62

OCSPP 

Guideline

Data 

Requirement 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed? Additional Comments 

835.6200 Aquatic field 

dissipation No data No Not triggered based on exposure aquatic toxicity profile.

850.1730 Fish 

bioconcentration No data No Low Kow indicates a low potential for bioaccumulation. 

850.6100 Analytical 

method in soil No data No All field dissipation studies were conducted prior to April 19, 

1996; therefore, Environmental 

Chemistry Method (ECM) and 

Independent Laboratory 

Validation (ILV) data are not 

required. 

850.6100 Analytical 

method in water

No data No 

Ecological Effects 

Tables 11 and 12 identify the ecological effects studies, as well as study classifications, and 

whether or not further data are anticipated to be needed in order to support risk assessment for 

registration review. The rationale for the additional data that EFED recommends be requested is 

presented within the tables. 
Page 30 of 62

Table11. Submitted Aquatic Ecological Effects Data for Myclobutanil 

OCSPP 

Guideline

Data Requirement 

Test Material 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed for 

risk 

assessment? 

Comments 

850.1010 Freshwater 

invertebrate 

acute toxicity 

00141678 Acceptable No 

None

850.1025

850.1035

Estuarine/saltwater 

invertebrate 

acute toxicity 

42747901 Supplemental No 

Controls did not meet the 

minimum shell growth 

requirement of 2 mm (1.4-

1.5 mm control shell growth 

reported) in the eastern 

oyster study (MRID 

42747901). Based on a 

review of data from other 

conazoles, mysid shrimp has 

predominantly been a more 

sensitive species than the 

eastern oyster and toxicity 

values were generally similar. 

As an acceptable mysid 

shrimp study is available, a 

new oyster study is not 

requested at this time.

42747902 Acceptable No See above

850.1075 Freshwater fish 

acute toxicity 

TGAI 

00144285 Acceptable Yes 

Under Guideline 850.1400, a

96-hour LC50 is required for 

the test species used in the 

freshwater early life stage 

study (fathead minnow). 

There is uncertainty with the 

available freshwater fish 

acute toxicity endpoint being 

the most sensitive species. 

Based on the most sensitive 

chronic fish study, it is 

recommended that the study 

be conducted using the 

fathead minnow. 

850.1075 Saltwater fish acute 

toxicity 42747903 Acceptable No None

850.1300 Freshwater 

invertebrate 

life cycle 

No data No 

NOAEC estimated using ACR 

for mysid shrimp acute and 

chronic toxicity data
Page 31 of 62

OCSPP 

Guideline

Data Requirement 

Test Material 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed for 

risk 

assessment? 

Comments 

850.1350 Estuarine/saltwater 

invertebrates 

life cycle 

47968901 Supplemental No 

Estimated EECs based on the 

label application rates and 

frequency are expected to 

exceed the upper limit of 

toxicity testing for this study. 

In the absence of additional 

toxicity data at higher dose 

ranges, the NOAEC of 0.0856 

mg a.i./L will be used. 

Although protective, this 

could have implications for 

future endangered species 

assessments due to the 

conservative nature of the 

endpoint and could lead to 

overly conservative risk 

assumptions. 

850.1735 Benthic 

invertebrates (acute) No data No 

Not triggered per 40 CFR Part 

158 based on chemical 

characteristics 

850.1740 Benthic 

invertebrates 

(chronic) 

No data No 

Not triggered per 40 CFR Part 

158 based on chemical 

characteristics– 

850.1400 Freshwater fish

early-life stage 

00164986/

40409201/ 

40480401 

Acceptable No 

As per 40 CFR, if a different 

test species is used for the 

chronic (early-life stage) data 

requirement than the acute 

study, a 96 hour LC50 must be 

provided. If the acute study 

(850.1075) is repeated with 

the fathead minnow as 

previously discussed, this 

requirement is fulfilled and 

an additional chronic study is 

not needed. 
Page 32 of 62

OCSPP 

Guideline

Data Requirement 

Test Material 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed for 

risk 

assessment? 

Comments 

850.1400 Estuarine/saltwater 

fish 

early-life stage 

No data No 

If data are provided as 

mentioned regarding the 

850.1400/850.1075 studies, 

NOAEC can be estimated 

using ACR for freshwater fish 

acute and chronic toxicity 

data in lieu of providing this 

study. 

850.1500 Fish life cycle

No data No 

Study not needed if 850.1400 

requirements for freshwater 

and saltwater fish are 

fulfilled. 

850.4400 Aquatic plant 

Toxicity Test Using 

Lemna spp. 

TEP 

No data Yes

No toxicity data are available 

for myclobutanil to address 

risks to vascular plants. 

Multiple incident reports 

have involved myclobutanil 

and plant species. 

850.4500 Algal Toxicity

TEP 41984801 Acceptable Yes 

Guidance recommends 

testing on four of the most 

sensitive nonvascular 

organisms whereas 

submitted data only includes 

one. Multiple incident 

reports have involved 

myclobutanil and plant 

species. 

850.4550 Cyanobacteria 

(Anabaena flosaquae) Toxicity 

TEP 

No data Yes 

Table 12. Submitted Terrestrial Ecological Effects Data for Myclobutanil 

OCSPP 

Guideline

Data Requirement

Test Material 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed for 

risk 

assessment? 

Comments 

850.2100 Avian oral toxicity 00144286 Acceptable Yes 
Page 33 of 62

OCSPP 

Guideline

Data Requirement

Test Material 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed for 

risk 

assessment? 

Comments 

TGAI 

No data for 

passerine 

Based on effects noted in 

the available toxicity data, 

and the potential for 

passerines to be more 

sensitive than the species 

previously tested, EFED 

recommends requesting a 

passerine study. 

850.2200 Avian dietary 

toxicity 

0144288 Acceptable No 

None

 850.2300 Avian reproduction 43087901 Supplemental No 

Estimated EECs based on 

the label application rates 

and frequency are expected 

to exceed the upper limit of 

toxicity testing for the avian 

reproduction study. In the 

absence of additional 

toxicity data at higher dose 

ranges, the NOAEC of 256 

mg a.i./kg diet will be used 

to estimate risks. Although 

protective, this could have 

implications for future 

endangered species 

assessments due to the 

conservative nature of the 

endpoint and could lead to 

overly conservative risk 

assumptions. 

Nonguideline Avian inhalation

No data No 

Based on STIR analysis, risks 

through inhalation pathway 

are not expected. 

81-1 

Acute mammalian 

oral LD50

(rat)

00165239/

00141662 Acceptable No None 

83-4 

Mammalian 

Reproduction

(rat)

00149581/

00143766 Acceptable No 

None
Page 34 of 62

OCSPP 

Guideline

Data Requirement

Test Material 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed for 

risk 

assessment? 

Comments 

850.3020 Honey bee adult 

acute contact 

toxicity 

00144289 Acceptable No 

Tier 1 toxicity test.

850.3030 Honey bee toxicity 

of residues on 

foliage None No 

This study is not triggered 

based on the reported 

endpoint in the honey bee 

adult acute contact study. 

Nonguideline 

OECD TG 

213 

Honey bee adult 

acute oral toxicity 

TGAI 

No data Yes 

Tier 1 toxicity test.

Nonguideline 

OECD TG 

237 

Honey bee larvae 

acute and chronic 

oral toxicity 

TGAI 

No data Yes 

Tier 1 toxicity test.

Nonguideline Honey bee adult 

chronic oral toxicity

TGAI 

No data Yes 

Tier 1 toxicity test.

Nonguideline 

OECD 

Guidance 

75 

Semi-field testing 

for pollinators 

TEP 

No data Yes 

Tier 2 test contingent on 

results of tier 1 tests and 

screening level residues. 

Nonguideline Field trial of 

residues in pollen 

and nectar 

TEP 

No data Yes 

Tier 2 test contingent on 

results of tier 1 tests and 

screening level residues. 

850.3040 Field testing for 

pollinators 

TEP 

No data Yes 

Tier 3 testing contingent on 

results of earlier tiers of 

testing. 
Page 35 of 62

OCSPP 

Guideline

Data Requirement

Test Material 

Submitted 

Studies 

(MRID) 

Study 

Classifications 

Are data 

needed for 

risk 

assessment? 

Comments 

850.4100 Terrestrial plant 

toxicity: 

Tier II seedling 

emergence 

TGAI 

No data Yes 

No toxicity data are 

available for myclobutanil 

to address risks to 

terrestrial plants. Multiple 

incident reports have 

involved myclobutanil and 

plant species. 850.4150 Terrestrial plant 

toxicity: 

Tier II vegetative 

vigor 

TEP 

No data Yes 

 
Page 36 of 62

Additional justification for non-guideline data requests: 

Study Title: Honeybee Acute Oral Toxicity, Adult 

Non-guideline Study, OECD 213 

Rationale for Requiring the Data 

Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use 

settings. With eusocial bees, pesticide residues may be transferred to pollen and/or nectar of 

treated plants and subsequently brought back to the hive. Therefore, potential acute effects to 

adult honeybees and other insect pollinators from oral exposure to some pesticides could exist. 

Currently available toxicity studies do not address possible effects of oral exposure on adult 

terrestrial insect survival. Because of the potential for pollen and nectar to be contaminated 

with pesticide residues, and subsequently brought back to the hive, it is important to determine 

the acute oral toxicity of this compound to adult honeybees and other insect pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for 

bees using the honeybee as a surrogate test species. The guidances discusses Tier I laboratorybased acute oral toxicity studies of individual adult bees as a critical component of the 

screening-level risk assessment process for examining potential adverse effects from specific 

routes of exposure. The guidance can be found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance. Additional guidance on the honeybee oral 

toxicity test design can be found in OECD Test Guideline 213 (http://www.oecdilibrary.org/docserver/download/9721301e.pdf?expires=1423074617&id=id&accname=guest&c

hecksum=2F0764FCB4DCF01D32382952A2E995C3) 

Practical Utility of the Data 

How will the data be used? 

The Tier 1 acute oral toxicity data on adult honeybees serve as a foundation for the screeninglevel assessment of potential risk non-target organisms such as federally listed threatened or 

endangered and non-listed terrestrial invertebrate insects, including pollinators, from acute oral 

exposures to pesticides. The data will be used to reduce uncertainties associated with the risk 

assessment for terrestrial invertebrates and will improve EPA’s understanding of the potential 

direct and indirect effects on a broad range of taxa. This study will also provide information with 

which to compare whether oral toxicity estimates differ from contact toxicity estimates 

obtained from other Tier 1 studies. If acute oral effects data for adult honey bees are not 

available, risks to terrestrial insects from acute oral exposure will be assumed.

How could the data impact the Agency’s future decision-making?

The data will inform the determination required under FIFRA or the ESA as to whether 

continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect listed threatened or endangered species and/or 

modify their designated critical habitat. Without these data, EPA may need to presume risk, 

which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could 

result in use restrictions. 
Page 37 of 62

Study Title: Honeybee Acute Oral Toxicity, Larvae 

Non-guideline Study, OECD 237 

Rationale for Requiring the Data 

Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use 

settings. With eusocial bees, pesticide residues may be transferred to pollen and/or nectar of 

treated plants and subsequently brought back to the hive where developing larvae and pupae 

may be exposed. Therefore, potential adverse effects to developing bees could result from 

exposure to pesticide residues. Available toxicity studies do not address possible effects on 

brood (larvae and pupae) survival/development. Because of the potential for pollen and nectar 

to be contaminated with pesticide residues, and subsequently brought back to the hive, it is 

important to determine the acute toxicity of this compound to bee brood. 

The Office of Pesticide Programs has made available a guidance regarding ecological testing for 

bees using the honeybee as a surrogate test species. The guidances discusses Tier I laboratorybased acute toxicity studies of individual honeybee larvae as a critical component of the 

screening-level risk assessment process for examining potential risks from specific routes of 

exposure. The guidance be found at: http://www2.epa.gov/pollinator-protection/pollinatorrisk-assessment-guidance. Additional guidance on larval honeybee toxicity test design can be 

found in OECD Test Guideline 237 (http://www.oecdilibrary.org/docserver/download/9713171e.pdf?expires=1422485600&id=id&accname=guest&c

hecksum=D8E07C2B1DF77BF096C3B29F55BF86A7). In some cases, information pertaining to 

acute toxicity to honey bee larvae may be obtained with the chronic honey bee larval test 

thereby negating the need for separate acute and chronic larval toxicity tests. 

Practical Utility of the Data 

How will the data be used? 

The Tier 1 acute toxicity data on honeybee larvae serve as a foundation for the screening-level 

assessment of potential risk to non-target organisms including federally listed threatened or 

endangered and non-listed terrestrial invertebrates, including pollinators, and/or modify their 

designated critical habitat from acute exposures to pesticides. The data will be used to reduce 

uncertainties associated with the risk assessment for terrestrial invertebrates and will improve 

EPA’s understanding of the potential effects on terrestrial species and whether there is a 

differential sensitivity of larval bees relative to adult bees. If acute effects data for larvae are 

not available, risks to terrestrial insects from acute exposure will be assumed.

How could the data impact the Agency’s future decision-making?

The data will inform the determination required under FIFRA or the ESA as to whether 

continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect listed threatened or endangered species and/or 

modify their designated critical habitat. Without these data, EPA may need to presume risk 

which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could 

result in use restrictions. 
Page 38 of 62

Study Title: Pollinator Chronic Oral Toxicity, Adult 

Non-guideline Study 

Rationale for Requiring the Data 

Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use 

settings. With eusocial bees, pesticide residues may be transferred to pollen and/or nectar of 

treated plants and subsequently brought back to the hive. Therefore, potential chronic effects 

to adult honeybees and other pollinators from oral exposure to some pesticides could exist. 

Currently available toxicity studies do not address possible lethal and sublethal effects of 

chronic oral exposure on adult terrestrial invertebrates and will assist in determining whether 

the sensitivity of adult bees differs from that of earlier life stages. Because of the potential for 

pollen and nectar to be contaminated with pesticide residues, and subsequently brought back 

to the hive, it is important to determine the chronic oral toxicity of this compound to adult 

honeybees and other pollinators.

The Office of Pesticide Programs has made available a guidance regarding ecological testing for 

bees using the honeybee as a surrogate test species. The guidances discusses Tier I laboratorybased chronic oral toxicity studies of individual adult honeybees as a critical component of the 

screening-level risk assessment process for examining potential risks from specific routes of 

exposure. The guidance can be found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance. Although study design elements for the 

chronic 10-day oral toxicity test with honey bees are similar to the OECD TG 213 acute oral 

toxicity test ( http://www.oecdilibrary.org/docserver/download/9721301e.pdf?expires=1422484908&id=id&accname=guest&c

hecksum=C38495D2A570AC2216CFB1F223D24AA7), EPA requests that the proposed protocol 

for this study be submitted for review and approval by EPA prior to initiating the test.

Practical Utility of the Data 

How will the data be used? 

The Tier 1 chronic toxicity data on adult bees serve as a foundation for the screening-level 

assessment of potential risk to non-target organisms including federally listed threatened or 

endangered species and non-listed terrestrial invertebrates, including pollinators, from chronic 

oral exposures to pesticides. The data will be used to reduce uncertainties associated with the 

risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the 

potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, 

particularly insect pollinators and to determine whether adult toxicity differs substantially from 

other life stages evaluated in other Tier 1 tests. If chronic oral effects data for adults are not 

available, risks to terrestrial insects from chronic exposure will be assumed.

How could the data impact the Agency’s future decision-making?

The data will inform the determination required under FIFRA or the ESA as to whether 

continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect listed threatened or endangered species and/or 

their designated critical habitat. Without these data, EPA may need to presume risk which will 
Page 39 of 62

limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in 

use restrictions. 

Study Title: Pollinator Chronic Oral Toxicity, Larvae 

Non-guideline Study 

Rationale for Requiring the Data 

Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use 

settings. For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of 

treated plants and subsequently brought back to the hive where larvae and pupae may be 

exposed. Therefore, potential effects to developing bees could result from chronic exposure 

to pesticide residues. Available toxicity studies do not address possible chronic effects on brood 

(larvae and pupae) survival. Because of the potential for pollen and nectar to be contaminated 

with pesticide residues, and subsequently brought back to the hive, it is important to determine 

chronic larval/pupal toxicity and whether adult emergence is adversely affected. This study will 

provide information on whether honeybee larvae differ in sensitivity from adult bees following 

chronic exposure. 

The Office of Pesticide Programs has made available a guidance regarding ecological testing for 

bees using the honeybee as a surrogate test species. The guidances discusses Tier I laboratorybased chronic toxicity studies of individual honeybee larvae as a critical component of the 

screening-level risk assessment process for examining potential risks from specific routes of 

exposure. The guidance can be found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance. Additional information on larval honeybee 

toxicity repeat exposure test design can be found in the OECD draft guidance 

(http://www.oecd.org/env/ehs/testing/Draft_GD_honeybees_rep_exp_for_2nd_CR_25_Novem

ber_2013.pdf). Although study design elements for the chronic 21-day toxicity test with honey 

bee larvae have been drafted, EPA requires that the proposed protocol for this study be 

submitted for review and approval by EPA prior to initiating the test. 

Practical Utility of the Data 

How will the data be used? 

The Tier 1 chronic toxicity data on bee larvae serve as a foundation for the screening-level 

assessment of potential risk to non-target organisms including federally listed threatened or 

endangered and non-listed terrestrial invertebrates, including insect pollinators, from chronic 

exposures to pesticides. These data will be used to reduce uncertainties associated with the 

risk assessment for terrestrial invertebrates and will improve EPA’s understanding of the 

potential direct and indirect lethal and sublethal effects on a broad range of terrestrial species, 

particularly insect pollinators. These data will also assist in determining whether early life stages 

of the bee differ in their sensitivity to pesticides relative to adults. If chronic effects data for 

larvae are not available, risks to terrestrial insects from chronic exposure will be assumed.

How could the data impact the Agency’s future decision-making?
Page 40 of 62

The data will inform the determination required under FIFRA or the ESA as to whether 

continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect listed threatened or endangered species and/or 

modify their designated critical habitat. Without these data, EPA may need to presume risk 

which will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could 

result in use restrictions. 

Study Title: Pollinator Tier II Semi-Field Toxicity Testing (tunnel/enclosure studies) 

Non-guideline Study, OECD 75 

Rationale for Requiring the Data 

Tier II studies are conditional on the outcome of the screening-level assessment where acute 

and/or chronic risk levels of concern have been exceeded for terrestrial invertebrates. 

Terrestrial invertebrates are likely to be impacted if exposed to pesticides in various use settings. 

For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated 

plants and subsequently brought back to the hive and may adversely affect developing brood 

(egg, larvae, and pupae) and adult bees. Screening-level (Tier 1) studies of individual bees do not 

address possible effects and/or exposure to pesticide residues at the colony-level. Because of 

the potential for pollen and nectar to be contaminated with pesticide residues, and subsequently 

brought back to the hive, it is important to determine whether bee colonies may be negatively 

affected under relatively controlled exposure conditions of a semi-field study. In addition to 

providing effects data, these studies can provide data on pesticide residues in pollen/nectar of 

treated plants. 

The Office of Pesticide Programs has made available a guidance regarding ecological testing for 

invertebrates with the honeybee. The guidance describes the tiered testing process and can be 

found at: http://www2.epa.gov/pollinator-protection/pollinator-risk-assessment-guidance . 

Additional information on honeybee colony studies under semi-field conditions can be found in the 

OECD Guidance 75 

http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono%28. 

Practical Utility of the Data 

How will the data be used? 

Tier II colony-level data will be used to assess potential risk to non-target organisms including 

listed and non-listed terrestrial social invertebrate species and to determine whether effects 

observed in the screening-level (Tier I) laboratory-based studies of individual bees are evident in 

colony-level studies under semi-field conditions. The Tier II semi-field test of whole colonies is a 

relatively controlled study, i.e., bees are confined to a specific area, that is designed to represent 

potential field-level exposure and account for hive dynamics, which are not achievable from 

other pollinator studies. This study will be used to determine whether adverse effects to insect 

pollinators at the whole colony level, may result for the use of pesticides and will help to refine 

risk estimates derived in the screening-level risk assessment for beneficial terrestrial 
Page 41 of 62

invertebrates. Measured residues in pollen/nectar can also be used to refine risk estimates 

derived from model-based or default values in the screening-level assessment. 

How could the data impact the Agency’s future decision-making?

The data will inform the determination required under FIFRA or the ESA as to whether continued 

registration of a pesticide is likely to result in unreasonable adverse effects to non-target species 

or is likely to adversely affect federally listed threatened or endangered species or their 

designated critical habitat. Without these data, EPA may need to presume risk which will limit 

the flexibility of pesticide products to comply with FIFRA and the ESA, and could result in 

significant use restrictions. 

Tier II Semi-Field Toxicity Testing for Pollinators (Feeding Studies) 

Rationale for Requiring the Data 

For eusocial bees, pesticide residues may be transferred to pollen and/or nectar of treated 

plants and subsequently brought back to the hive and may adversely affect developing brood 

(egg, larvae, and pupae) and adult bees. Tier II feeding studies are conditional on the 

outcome of the screening-level assessment where acute and/or chronic risk levels of concern 

have been exceeded for terrestrial invertebrates based on Tier I studies of individual bees. 

Feeding studies utilize free foraging bee colonies that are “dosed” with specific quantities of 

test material and represent a means of ensuring exposure to the test material through spiked 

pollen and/or sugar solutions fed to the colony while still allowing the bees to forage freely. 

Since bee colonies are not confined to enclosures, colonies can be exposed for longer 

duration periods without subjecting the bees to stress that typically results from Tier II tunnel 

studies. Available toxicity studies of individual bees (Tier 1) conducted to support screeninglevel assessments do not address possible effects and/or exposure to pesticide residues at 

the colony-level. It is therefore important to determine whether bee colonies may be 

negatively affected where bees are free foraging and have the option to collect/consume 

alternative forage items beyond the spiked food. Since multiple dose levels can be more 

readily tested, feeding studies can help to define dose-response relationships at the whole 

colony level. 

The Office of Pesticide Programs has made available a guidance regarding ecological testing 

for invertebrates with the honeybee. The guidance describes the tiered testing process and 

can be found at: http://www2.epa.gov/pollinator-protection/pollinator-risk-assessmentguidance . Additional information on honeybee colony studies under semi-field conditions 

can be found in the OECD Guidance 75 

http://www.oecd.org/officialdocuments/publicdisplaydocumentpdf/?cote=env/jm/mono%28

. 

Practical Utility of the Data 

How will the data be used? 

Tier II colony feeding data will be used to assess potential risk to non-target organisms 

including listed and non-listed terrestrial social invertebrate species. The colony feeding 

study is designed to represent potential field-level exposure and account for hive dynamics 
Page 42 of 62

using longer duration exposure periods than are possible in Tier II tunnel studies. This study 

will be used to determine whether potential adverse effects to insect pollinators at the whole 

colony level when bees are able to forage naturally beyond the spiked food. Results from the 

feeding study will help to refine the screening-level risk assessment for beneficial terrestrial 

invertebrates that were based on Tier I studies on individual bees. Since feeding studies can 

help to define a dose-response relationship at the colony level, the studies can provide a 

means of determining exposure thresholds below which the likelihood of adverse effects on 

colonies may be low. 

How could the data impact the Agency’s future decision-making?

The Tier II colony-level data will be used to refine screening-level risk estimates derived using 

Tier I laboratory-based data on individual bees. The Tier II data will help to inform the 

determination required under FIFRA or the ESA as to whether continued registration of a 

pesticide is likely to result in unreasonable adverse effects to non-target species or is likely to 

adversely affect federally listed threatened or endangered species or their designated critical 

habitat. Without these data, EPA may need to presume risk which will limit the flexibility of 

pesticide products to comply with FIFRA and the ESA, and could result in significant use 

restrictions. 

Field Testing for Pollinators 

OCSPP Guideline 850.3040 

Rationale for Requiring the Data 

Tier III studies are conditional on the outcome of the screening-level assessment (Tier 1) 

where acute and/or chronic risk levels of concern have been exceeded for terrestrial 

invertebrates and where Tier II studies either under semi-field tunnel conditions and/or 

feeding studies have indicated potential adverse effects at the colony level. Available toxicity 

studies from lower-tier studies do not address possible effects and/or exposure to pesticide 

residues at the colony-level under actual pesticide use conditions and where specific 

uncertainties regarding the likelihood of exposure and/or effects remain. Full-field studies 

also provide an opportunity to measure residues in pollen and nectar as well as various 

matrices (beebread, honey, wax) within the colony to obtain a more realistic understanding 

of exposure. 

The Office of Pesticide Programs has made available a guidance regarding ecological testing for 

terrestrial invertebrates using the honeybee as a surrogate test species. The guidance 

discusses Tier I laboratory-based acute oral toxicity studies of individual adult bees as a critical 

component of the screening-level risk assessment process for examining potential adverse 

effects from specific routes of exposure. The guidance can be found at: 

http://www2.epa.gov/pollinator-protection/pollinator-risk-assessment-guidance . Additional 

guidance on the honeybee oral toxicity test design can be found in OECD Test Guideline 213 

http://www.oecd-ilibrary.org/environment/test-no-213-honeybees-acute-oral-toxicitytest_9789264070165-en.

Practical Utility of the Data 
Page 43 of 62

How will the data be used? 

Tier III colony-level data will be used to further characterize potential risk to non-target 

organisms including listed and non-listed terrestrial social invertebrate species and to refine 

screening-level risk estimates that were based on individual bee responses. The semi-field 

test is a controlled study that is designed to represent potential field-level exposure under 

relatively controlled conditions and account for hive dynamics, which are not achievable from 

lower-tier pollinator studies. This study will be used to determine whether adverse effects to 

insect pollinators at the whole colony level, may result for the use of pesticides and will help 

to refine the screening-level risk estimates for beneficial terrestrial invertebrates. This study 

will also be used to determine whether more refined (Tier 3) studies are needed to 

characterize risk. 

How could the data impact the Agency’s future decision-making?

The data will inform the determination required under FIFRA or the ESA as to whether 

continued registration of a pesticide is likely to result in unreasonable adverse effects to nontarget species or is likely to adversely affect federally listed threatened or endangered species 

or their designated critical habitat. Without these data, EPA may need to presume risk which 

will limit the flexibility of pesticide products to comply with FIFRA and the ESA, and could 

result in significant use restrictions. 

Study Title: Field Trial of Residues in Pollen and Nectar 

Non-guideline Study 

Rationale for Requiring the Data 

Terrestrial invertebrates are likely to be impacted if exposed to pesticides residues in various use 

settings. Pesticide residues may be transferred to pollen and/or nectar of treated plants and 

subsequently brought back to hive all life stages may be exposed. For some pesticides, the 

quantification of pollinator-relevant residues in treated flowering plants is needed, since 

pollinators will be exposed to residues from either current or prior season applications (due to 

the potential for residues to accumulate in plants and trees). Residues in edible/transportableto-hive parts of treated trees and plants, including (where appropriate), but not limited to, 

guttation water, sap/resins, whole plant tissue (e.g., leaves, stems), as well as blooming, pollenshedding, and nectar producing parts (i.e., flowers and, if present, extra-floral nectaries) of 

plants may inform the potential for risk. Studies should be designed to provide residue data for 

crops and application methods of concern. 

The Office of Pesticide Programs has made available a guidance regarding ecological testing for 

bees using the honeybee as a surrogate. This can be found at: http://www2.epa.gov/pollinatorprotection/pollinator-risk-assessment-guidance. Since residue studies are intended to provide 

exposure data in multiple matrices and under specific application conditions, EPA requests that 

the protocol is submitted for review and approval by EPA prior to initiation of the study.

Practical Utility of the Data 
Page 44 of 62

How will the data be used? 

Measured residue data will be used to refine conservative estimates of pesticide exposure and 

reduce uncertainties associated with the Tier I exposure assessment by providing direct 

measurements of pesticide concentrations resulting from actual use settings. Measured residues 

may provide a more realistic understanding of exposure through contact or ingestion with which 

to calculate risk quotients for individual bees as well as to characterize exposure to the colony. If

measured residue data are not available, risk estimates for terrestrial insects will be based on 

model generated or default values used to support the screening-level assessment.

How could the data impact the Agency’s future decision-making?

The data will inform the determination required under FIFRA or the ESA as to whether continued 

registration of a pesticide is likely to result in unreasonable adverse effects to non-target species 

or is likely to adversely affect federally listed threatened or endangered species or their 

designated critical habitat. Without these data, EPA will have to rely on conservative estimates 

of exposure which may limit the flexibility of pesticide products to comply with FIFRA and the 

ESA, and could result in use restrictions. 

 
Page 45 of 62

References 

FAO 2000. Appendix 2. Parameters of pesticides that influence processes in the soil. In FAO 

Information Division Editorial Group (Ed.), Pesticide Disposal Series 8. Assessing Soil 

Contamination. A Reference Manual. Rome: Food & Agriculture Organization of the United 

Nations (FAO). http://www.fao.org/docrep/003/x2570e/x2570e00.htm 

Duah, F.K, Fisher, J.M., Halder, C.A., Hall, L.R., Hall, T.A., Kelley, I., Tolliver, M.K. and Van 

Goethem, D. L., 2001. An Overview of the Available Data on 1,2,4-Triazole [Cas No. 288-88-0], a 

degradate of the Azole Class of Fungicides, and its Relevance to the Risk Profile of Tebuconazole 

(FOLICURTM). Bayer Corporation. February 27, 2001. 

USEPA. 2006 a. 1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid: Drinking Water Assessment 

in Support of Reregistration and Registration Actions for Triazole-derivative Fungicide 

Compounds. D320682. Office of Pesticide Programs Environmental Fate and Effects Division, 

Environmental Risk Branch 1. February 28, 2006. 

USEPA. 2006 b. 1,2,4-Triazole, Triazole Alanine, Triazole Acetic Acid: Human Health Aggregate 

Risk Assessment in Support of Reregistration and Registration Actions for Triazole-derivative 

Fungicide Compounds. DP Number 322215. Office of Pesticide Programs Health Effects Division 

and Environmental Fate and Effects Division. February 7, 2006. 

USEPA. 2012 a. Drinking Water Exposure Concentrations for Proposed New Myclobutanil Uses 

on Grass Grown for Seed, Grass Pastures, Rangeland, and Sod Farms. D403754. Office of 

Pesticide Programs Environmental Fate and Effects Division, Environmental Risk Branch 3. 

November 20, 2012. 

USEPA. 2012 b. Development and Use of Percent Cropped Area and Percent Turf Area 

Adjustment Factors in Drinking Water Exposure Assessments: 2012 Update. Office of Pesticide 

Programs Environmental Fate and Effects Division. May 16, 2012. 

USEPA. 2012 c. NAFTA Guidance for Evaluating and Calculating Degradation Kinetics in 

Environmental Media. December 17, 2012. U.S. Environmental Protection Agency, Office of 

Pesticide Programs, Environmental Fate and Effects Division. Arlington, VA. 

USEPA. 2012 d. Standard Operating Procedure for Using the NAFTA Guidance to Calculate 

Representative Half-life Values and Characterizing Pesticide Degradation. November 30, 2012. 

U.S. Environmental Protection Agency, Office of Pesticide Programs, Environmental Fate and 

Effects Division. Arlington, VA. 

USEPA 2014 a. Guidance for Assessing Pesticide Risks to Bees. Office of Pesticide Programs. June 

23, 2014. 

http://www.epa.gov/pesticides/science/efed/policy_guidance/team_authors/terrestrial_biolog

y_tech_team/GuidanceAssessingPesticideRisk2Bees.pdf
Page 46 of 62

USEPA 2014 b. Myclobutanil Label Use Information System (LUIS) Report. Biological and 

Economic Analysis Division. 

USEPA 2014 c. Myclobutanil Summary Level Usage Analysis (SLUA). Biological and Economic 

Analysis Division. 

Vogel, J.R., M.S. Majewski, and P.D. Capel., 2008. Pesticides in Rain in Four Agricultural 

Watersheds in the United States. J. Env. Qual. 37:1101-1115.
Page 47 of 62

Appendix A. Myclobutanil Transformation Products Table A1. Myclobutanil, its Major Transformation Products, and 1,2,4-Triazole Conjugates of Toxicological Con

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID 

(% 

D

D

PARENT

Myclobutanil IUPAC Name: 2-(4-chlorophenyl)-2-(1H1,2,4-triazol-1-ylmethyl)hexanenitrile

CAS Number: 88671-89-0

Molecular Weight: 288.775299 g/mol

Chemical Formula: C15H17ClN4SMILES: CCCCC(CN1C=NC=N1)(C#N)C2=CC=C(C=C2)Cl

Parent structure sho

MAJOR TRANSFORMATION PRODUCTS

1,2,4-Triazole IUPAC Name: 

4H-1,2,4-triazole Molecular Weight: 69.0653 g/mol Chemical Formula: C2H3N3

SMILES: C1=NN=CN1 

Aqueous photolysis 164560 40319801 Aerobic soil metabolism 

141680 164561 18

Terrestrial field Dissipation 

00164563

00164987

0-

3-

6-1

0-3” 1603-6” 
Page 48 of 62

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID 

(% 

D

D

6-12

1,2,4-TRIAZOLE CONJUGATES OF TOXICOLOGICAL CONCERN 

1,2,4-Triazole Alanine 

IUPAC Name: 2-amino-3-(1H-1,2,4-triazol-1-yl)propanoic acid

Chemical Formula: C5H8N4O2

Molecular Weight: 156.143 SMILES: NC(CN1C=NC=N1)C(O)=O 1,2,4-Triazole Conjugates Not Id

1,2,4-Triazole Available FatAcetic Acid 

IUPAC Name: 2-(1H-1,2,4-triazol-1-yl)acetic acid

Chemical Formula: C4H5N3O2

Molecular Weight: 127.038 SMILES: c1ncn(n1)CC(=O)O

*Maximum % of applied reported at study termination; amounts may have continued to increase with time

Bold indicates maximum % formation percentage of degradate 
Page 49 of 62

Table A2. 1,2,4-Triazole, its Major Transformation Products, and its Conjugates of Toxicological Concern. 

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID 

(% 

D

D

PARENT

1,2,4-Triazole IUPAC Name: 

4H-1,2,4-Triazole Molecular Weight: 69.0653 g/mol Chemical Formula: C2H3N3

SMILES: C1=NN=CN1 

Parent Structure Show

1,2,4-TRIAZOLE CONJUGATES OF TOXICOLOGICAL CONCERN

1,2,4-Triazole Alanine 

IUPAC Name: 2-amino-3-(1H-1,2,4-triazol-1-yl)propanoic acid

Chemical Formula: C5H8N4O2

Molecular Weight: 156.143 SMILES: NC(CN1C=NC=N1)C(O)=O 

anaerobic soil metabolism 45930701

(7 

t

1,2,4-Triazole Acetic Acid 

IUPAC Name: 2-(1H-1,2,4-triazol-1-yl)acetic acid

aerobic soil metabolism 45297203 
Page 50 of 62

Code Name/ Synonym Chemical Name Chemical Structure Study Type MRID 

(% 

D

D

Chemical Formula: C4H5N3O2

Molecular Weight: 127.038 SMILES: c1ncn(n1)CC(=O)O

1

45284038

< 

45284032

6

1

0

anaerobic soil metabolism 45930701 

MAJOR NON-CONJUGATE TRANSFORMATION PRODUCTS

Hydroxytriazole

IUPAC Name: 

1H-1,2,3-triazol-1-ol Molecular Weight: 85.065 Chemical Formula: C2H3N3O 

SMILES: On1nncc1

aerobic soil metabolism 

45284038

3

45284032

12

*Maximum % of applied reported at study termination; amounts may have continued to increase with time

Bold indicates maximum % formation percentage of degradate 
Page 51 of 62

Appendix B. SIP analysis inputs and results 

Table B1. Inputs Parameter Value Chemical name Myclobutanil Solubility (in water at 25oC; mg/L) 142 Mammalian LD50 (mg/kg-bw) 1360 Mammalian test species other Body weight (g) of "other" mammalian species 20 Mammalian NOAEL (mg/kg-bw) 16 Mammalian test species laboratory rat Body weight (g) of "other" mammalian species Avian LD50 (mg/kg-bw) 498 Avian test species northern bobwhite quail Body weight (g) of "other" avian species Mineau scaling factor 1.15 Mallard NOAEC (mg/kg-diet) 1250 Bobwhite quail NOAEC (mg/kg-diet) 256 NOAEC (mg/kg-diet) for other bird species Body weight (g) of other avian species NOAEC (mg/kg-diet) for 2nd other bird species Body weight (g) of 2nd other avian species Enter body weight of 'other' mammalian species for LD50. 
Page 52 of 62

Table B2. Mammalian Results Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 24.4240 24.4240 Adjusted toxicity value (mg/kg-bw) 511.4420 12.3066 Ratio of exposure to toxicity 0.0478 1.9846 Conclusion* 

Drinking water exposure 

alone is NOT a potential 

concern for mammals 

Exposure through 

drinking water alone is 

potential concern for 

mammals 

Table B3. Avian Results Parameter Acute Chronic Upper bound exposure (mg/kg-bw) 115.0200 115.0200 Adjusted toxicity value (mg/kg-bw) 358.7739 27.2124 Ratio of exposure to acute toxicity 0.3206 4.2268 Conclusion* 

Exposure through 

drinking water alone is a 

potential concern for 

birds 

Exposure through 

drinking water alone is 

potential concern for 

birds 

*Conclusion is for drinking water exposure alone. This does not combine all routes of exposure. Therefore, when aggregated with other routes (i.e., diet, inhalation, dermal), pesticide exposure through drinking water may contribute ta total exposure that has potential for effects to non-target animals. 
Page 53 of 62

Appendix C. STIR analysis results 

Welcome to the EFED 

Screening Tool for Inhalation Risk 

This tool is designed to provide the risk assessor with a rapid method for determining the potential 

significance of the inhalation exposure route to birds and mammals in a risk assessment. 

 

Input 

Application and Chemical Information 

Enter Chemical Name Myclobutanil 

Enter Chemical Use Fungicide 

Is the Application a Spray? (enter y or n) y 

If Spray What Type (enter ground or air) ground 

Enter Chemical Molecular Weight (g/mole) 288.78 

Enter Chemical Vapor Pressure (mmHg) 9.75E-06 

Enter Application Rate (lb a.i./acre) 1.4 

 

Toxicity Properties 

Bird 

Enter Lowest Bird Oral LD50 (mg/kg bw) 498 

Enter Mineau Scaling Factor 1.15 

Enter Tested Bird Weight (kg) 0.178 

Mammal 

Enter Lowest Rat Oral LD50 (mg/kg bw) 1360 

Enter Lowest Rat Inhalation LC50 (mg/L) 2.07 

Duration of Rat Inhalation Study (hrs) 4 

Enter Rat Weight (kg) 0.35 

 

Output 

Results Avian (0.020 kg ) 

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.52E-01 

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 1.90E-02 

Adjusted Inhalation LD50 4.23E+00 

Ratio of Vapor Dose to Adjusted Inhalation LD50 4.51E-03 Exposure not Likely Significant 

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 1.48E-01 

Ratio of Droplet Inhalation Dose to Adjusted Inhalation 

LD50 3.50E-02 Exposure not Likely Significant 

 

Results Mammalian (0.015 kg ) 

Maximum Vapor Concentration in Air at Saturation 

(mg/m3) 1.52E-01 
Page 54 of 62

Maximum 1-hour Vapor Inhalation Dose (mg/kg) 2.39E-02 

Adjusted Inhalation LD50 1.23E+02 

Ratio of Vapor Dose to Adjusted Inhalation LD50 1.94E-04 Exposure not Likely Significant 

Maximum Post-treatment Spray Inhalation Dose (mg/kg) 1.86E-01 

Ratio of Droplet Inhalation Dose to Adjusted Inhalation 

LD50 1.51E-03 Exposure not Likely Significant 

 

 
Page 55 of 62

Appendix D. Toxicity comparison for myclobutanil and degradates 

Table D1. Additional Toxicity Endpoints for Myclobutanil Degradates (1,2,4-triazole, triazole 

alanine and triazole acetic acid)1 

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

1,2,4-triazole (aquatic toxicity) 

Freshwater 

fish 

Acute 

Rainbow 

trout 

 (Salma 

gairdneri) 

96-hr LC50= 760 

mg a.i./L 

00133380/4528

4017 Under Review 

Chronic (28 day 

growth toxicity 

test) 

Rainbow 

trout 

(Oncorhynchu

s mykiss) 

LC50: > 100 mg/L 

NOAEC (growth) ≥ 

100 mg/L 

NOAEC (sublethal 

effects) = 3.2 

mg/L 

LOAEC (sublethal 

effects) = 10.0 

mg/L 

Observed 

sublethal effects 

included multiple 

fish being inactive 

or displaying 

abnormally low 

activity, labored 

respiration, and 

lying inactive on 

the bottom of the 

aquarium in the 

three highest 

concentrations 

tested between 

days 23 and 

28. 

45880405 

(Supplemental) 

Supplemental due to 

non-guideline study 

Acute 

Rainbow 

Trout (Salmo 

gairdneri) 

96 hr-LC50 = 498 

mg ai/L 

NOAEC = 378 mg 

ai/L 

(mortality) 

48474301 

(Acceptable) None 
Page 56 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

Freshwater 

Invertebrat

es 

Acute 

Water flea 

(Daphnia 

magna) 

 LC50 = 900 (730 to 

2200, 95% C.I.) 

mg/L. 

00133381 Under Review 

Acute 

Water flea 

(Daphnia 

magna)

48-hr EC50 > 98.1 

mg ai/L 

NOAEC = 98.1 mg 

ai/L (based on 

mobility, highest 

concentration 

tested) 

48453206 

(Acceptable) None 

Aquatic 

Plants - 

Non 

vascular 

Acute 

Freshwater 

Algae 

(Pseudokirch

neriella 

subcapitata, 

formerly 

Selenastrum 

capricornutu

m)

96-hr endpoints: 

Biomass (most 

sensitive): 

EC50 = 14 mg ai/L 

NOAEC = 3.1 mg 

ai/L 

Cell Density: 

EC50 = 18 mg ai/L 

NOAEC = 6.8 mg 

ai/L 

Growth Rate: 

EC50 > 31 mg ai/L 

NOAEC = 6.8 mg 

ai/L 

45880401 

(Acceptable) None

 Acute 

Green algae 

(Scenedesmu

s subspicatus) 

EC50 = 6.3 (5.5 to 

7.1, 95% C.I.) 

mg/L 

00133382 Under Review 

1,2,4-triazole (terrestrial toxicity) 

Birds 

 Acute Coturnix 

quail

LD50 >316 mg /kg 

bw 45284015 Under Review

 Acute 

Bobwhite 

quail 

(Colinus 

virginianus) 

LD50 = 770 mg /kg 

bw 49380701 Under Review 

Mammals Acute 

Laboratory 

mouse (Mus 

musculus)

LD50 = 3650 

mg/kg 45284001 Review not available2 

 Acute Laboratory 

Rat (M) 

LD50 = 1375 

mg/kg 45284008 Reviews not 

available2
Page 57 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

(Rattus 

norvegicus)

LD50 = 1648-3080 

mg/kg 

45284004, 

45284001 

Reproduction and 

fertility effects

0, 250, 500, 3000 

ppm 

M: 15, 31, 189 

mkd 

F: 18, 36, 218 mkd 

Laboratory 

rat (Rattus 

norvegicus)

Parental 

NOAEC/NOAEL 

<250 ppm/15 

mg/kg/day 

Parental 

LOAEC/LOAEL= 

250 ppm/15 

mg/kg/day based 

on decrease in 

bodyweight, 

bodyweight gain 

and spleen 

weight. 

Offspring 

NOAEC/NOAEL= 

<250 ppm/19 

mg/kg/day 

Offspring 

LOAEC/LOAEL= 

250 ppm/19 

mg/kg/day based 

on decrease in 

bodyweight, 

bodyweight gain, 

brain and spleen 

weights 

Repro 

NOAEC/NOAEL= 

250 ppm/15 

mg/kg/day 

Repro 

LOAEC/LOAEL= 

500 ppm/31 

mg/kg/day based 

on abnormal 

sperm and ↓# of 

CL in F1 females 

At 3000 ppm/218 

mg/kg/day, 

reproductive 

failure (no viable 

offspring), ↑CL in 

F0 parental 

females

46467304 

(Acceptable) None 
Page 58 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

Developmental 

Toxicity in Rabbits 

0,5,15,30,45 

mg/kg/day 

New Zealand 

white rabbit 

Parental/develop

mental NOAEL= 

30 mg/kg/day 

Parental/develop

mental LOAEL= 45 

mg/kg/day based 

on mortality and 

clinical signs 

(decreased motor 

activity, head tilt, 

lacrimation, 

drooping eyelids, 

diarrhea and 

salivation) for 

parental effects 

and decreased 

fetal weight and 

urinary tract 

malformations for 

developmental 

effects 

Mortality (6/25 

rabbits) in 45 

mg/kg/day group 

46492903 

(Acceptable) None 

Terrestrial 

Invertebrat

es 

Acute and 

reproductive (28 

days) 

Collembolan 

(springtails) 

Species 

(Folsomia 

candida) soil 

arthropods 

LC50>10 mg/kg 

NOAEC 

(mortality) ≥ 

10mg/kg 

NOAEC 

(reproduction) = 

1.8 mg/kg 

45880404 

(Supplemental) Non-guideline study 

Growth and 

reproductive (8 

weeks, adult 28 

day exposure, 

additional 4 week 

offspring 

exposure) 

Earthworms 

(Eisenia 

fetida)

LC50> 70.81 ug/kg 

NOAEC ≥ 70.81 

ug/kg (highest 

concentration 

tested) 

No significant 

treatment effects 

for mortality, 

behavior, body 

weights, 

reproduction or 

food consumption 

45880402 

(Supplemental) Non-guideline study 

Triazole alanine (aquatic toxicity) 
Page 59 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

No submitted data identified 

Triazole alanine (terrestrial toxicity) 

Mammals 

90-day oral toxicity 

in rodents – rat 

0, 1250, 5000, 

20000 ppm 

M: 0, 90, 370, 

1510 mg/kg/day 

F: 0,160, 400, 1680 

mg/kg/day 

Laboratory 

rat 

(Rattus 

norvegicus)

NOAEL = 90/160 

mg/kg/day (M/F) 

LOAEL = 370/400 

mg/kg/day (M/F) 

based on 

decreased 

leukocyte counts 

and decreased 

triglycerides in 

females 

At 1510/1680 

mg/kg/day (M/F) 

decreased body 

weight (M), body 

weight gain (M), 

leukocytes (M/F) 

and triglycerides 

(M/F) 

00164107 

(Acceptable) None 

Reproduction and 

fertility effects

0, 200, 2000, 

10000 ppm 

M: (F0/F1) 0, 

50/47, 213/192, 

1098/929 

mg/kg/day 

F: 0, 51/49, 

223/199, 

1109/988 

mg/kg/day 

Laboratory 

rat 

(Rattus 

norvegicus)

Parental 

NOAEC/NOAEL= 

10000 ppm/929 

mg/kg/day 

Parental 

LOAEC/LOAEL: 

>10000 

ppm/929mg/kg/d

ay 

Offspring 

NOAEC/NOAEL 

<250 ppm/19 

mg/kg/day 

Offspring 

LOAEC/LOAEL=20

00ppm/192 

mg/kg/day based 

on reduced mean 

litter weights in 

both generations 

 Repro 

LOAEC/LOAEL>10

000 

00164112 

(Acceptable) None 
Page 60 of 62

Taxonomic 

Group Study type 

Surrogate 

Species Toxicity 

MRID 

(classification) Comments 

ppm/929mg/kg/d

ay

Triazole acetic acid (aquatic toxicity) 

Freshwater 

Fish Acute 

Rainbow 

trout 

(Oncorhynchu

s mykiss) 

96 hr-LC50 >101 

mg ai/L 

NOAEC = 101 mg 

ai/L 

(mortality/sublethal effects) 

48453209 

(Acceptable) None 

Freshwater 

Invertebrat

es 

Acute 

Water flea 

(Daphnia 

magna)

48-hr EC50 > 108 

mg ai/L 

NOAEC = 108 mg 

ai/L 

(based on 

mobility, highest 

concentration 

tested) 

48453208 

(Acceptable) None 

Triazole acetic acid (terrestrial toxicity)

Mammals Acute 

Laboratory 

rat 

(Rattus 

norvegicus)

LD50 > 5000 

mg/kg 45596802 Review not available2

14 day oral toxicity 

in rodents 

0, 100, 1000, 8000 

ppm 

M: 0, 10.6, 102.8, 

788.3 mg/kg/day 

F: 0, 10.1, 97.2, 

703.5 mg/kg/day 

Laboratory 

rat 

(Rattus 

norvegicus)

NOAEL = 

788.3/703.5 

mg/kg/day 

(M/F) 

LOAEL 

>788.3/>703.5 

mg/kg/day (M/F) 

45596801 None 

1 Many endpoints derived from summary document USEPA 2006 b. 1,2,4-Triazole, Triazole 

Alanine, Triazole Acetic Acid: Human Health Aggregate Risk Assessment in Support of 

Reregistration and Registration Actions for Triazole-derivative Fungicide Compounds. 

2 Values taken from triazole aggregate study referenced above, where it was noted that some 

values were from submitted summary data and full study reports were not available. 

 
Page 61 of 62

Table D2. Summary table of comparable toxicity data for myclobutanil and major degradate 

1,2,4-triazole and its conjugates triazole alanine and triazole acetic acid1 

Taxonomic group Study type Myclobutanil 1,2,4-triazole Triazole 

Alanine 

Triazole 

acetic acid

Freshwater fish Acute

96-hr LC50

2.4 mg/L

(Bluegill sunfish) 

498 mg/L

(rainbow trout)

>101 mg/L

Chronic NOAEC =0.98 mg/L

(fathead minnow) 

3.2 mg/L

(rainbow trout)

Estuarine/marine fish

(sheepshead minnow)

Acute

96-hr LC50

4.7 mg/L

Chronic --

Freshwater 

Invertebrates 

(water flea) 

Acute

48-hr EC50

11 mg/L > 98.1 mg/L >108 mg/L

Chronic NOAEC = 3.9 mg/L 

(based on ACR 

analysis) 

Estuarine/marine 

invertebrates 

(mysid shrimp) 

Acute

96-hr LC50

0.24 mg/L

Chronic NOAEC = 0.0856 

mg/L 

(LOAEC > 0.0856 

mg/L, no effects 

seen) 

Aquatic Plants

(Green algae) 

120-hr EC50 0.83 mg/L 6.3 mg/L

Birds

(Bobwhite quail) 

Acute

LD50

498 mg/kg bw 770 mg/kg bw

Chronic NOAEC = 256 mg/kg 

diet 

(LOAEC >256 mg/kg 

diet, no effects 

seen) 

Mammals Acute 

(mouse LD50) 

1360 mg/kg bw 3650 mg/kg bw >5000 

mg/kg bw

Acute 

(rat LD50) 

1600 mg/kg bw 1375 mg/kg bw

Chronic

(rat NOAEL) 

16 mg/kg bw 15 mg/kg bw 703.5 

mg/kg bw

19 mg/kg 

bw 

1

See Tables 7-9 for individual study details. 
Page 62 of 62

Table D3. Comparison of ECOSAR outputs for myclobutanil and major degradate 1,2,4-triazole (and its conjugates triazacetic acid) and hydroxytriazole 

Taxonomic group Study type1 

Myclobutanil Myclobutanil Myclobut anil 1,2,4- triazole Triazole Alanine Triazol

Acetic A

Study Value 

(mg/L) 

ECOSAR Class: 

Benzyl Nitriles 

(mg/L) 

ECOSAR Class: Triazoles (Non-fused

Freshwater fish 96-hr LC50 2.4 10.9 33 3574.08 3.97 x 107* 3.96 x 1

Chronic Value NOAEC = 0.98 1.73 0.116 2.465 5279.28 169.42 

Estuarine/marine fish 

96-hr LC50 4.7 17.4 96.423 14610.51 2.28 x 108* 1.79 x 10Chronic Value -- -- 0.189 0.350 63.34 11.77 

Freshwater Invertebrates 

96-hr LC50 11 110 9.9 49.73 24526.29 2234.2Chronic Value NOAEC = 3.9 

(based on ACR 

analysis) 

1.059 0.966 22.77 53985.50 1611.6

Estuarine/marine invertebrates 

96-hr LC50 0.24 1.086 9.612 1309.41 1.84 x 107* 1.55 x 1Chronic Value NOAEC = 0.0856

(LOAEC > 0.0856, 

no effects seen) -- 14.987 126000 1.15 x 1011* 4.99 x 10

Aquatic plants (green algae) 

96-hr LC50 0.83 2.568 5.762 79.46 1.09 x 105* 4806.5Chronic Value -- 1.562 5.074 59.008 68398.53 3395.2

* = asterisk designates: Chemical may not be soluble enough to measure this predicted effect. If the effect level exceed

10X, typically no effects at saturation (NES) are reported. 

1 Chronic values not available for some taxonomic groups